U.S. patent application number 12/991564 was filed with the patent office on 2011-05-19 for carbamoyl derivatives of bicyclic carbonylamino-pyrazoles as prodrugs.
This patent application is currently assigned to NERVIANO MEDICAL SCIENCES S.R.L.. Invention is credited to Paolo Polucci, Maurizio Pulici.
Application Number | 20110118278 12/991564 |
Document ID | / |
Family ID | 40886839 |
Filed Date | 2011-05-19 |
United States Patent
Application |
20110118278 |
Kind Code |
A1 |
Pulici; Maurizio ; et
al. |
May 19, 2011 |
CARBAMOYL DERIVATIVES OF BICYCLIC CARBONYLAMINO-PYRAZOLES AS
PRODRUGS
Abstract
There are provided bicyclic carbonylamino-pyrazoles of formula
(I), wherein the variables are as specified in the claims, for use
as medicament, in particular for the treatment of diseases due to
the malfunctioning of protein kinases (PKs), such as cancer,
pharmaceutical compositions comprising such carbamoyl derivatives,
and their use as prodrugs of therapeutically active agents. Method
of treatment and some new bicyclic carbonylamino-pyrazoles are also
object of the present invention. ##STR00001##
Inventors: |
Pulici; Maurizio; (Caponago,
IT) ; Polucci; Paolo; (Cassina Rizzardi (CO),
IT) |
Assignee: |
NERVIANO MEDICAL SCIENCES
S.R.L.
Nerviano (MI)
IT
|
Family ID: |
40886839 |
Appl. No.: |
12/991564 |
Filed: |
May 14, 2009 |
PCT Filed: |
May 14, 2009 |
PCT NO: |
PCT/EP09/55802 |
371 Date: |
November 8, 2010 |
Current U.S.
Class: |
514/253.04 ;
514/254.06; 514/322; 514/407; 544/362; 544/371; 546/199;
548/360.5 |
Current CPC
Class: |
A61P 17/06 20180101;
A61K 31/496 20130101; A61P 13/08 20180101; A61P 13/12 20180101;
A61P 11/00 20180101; A61P 43/00 20180101; C07D 487/04 20130101;
C07D 471/04 20130101; A61K 31/454 20130101; C07D 231/56 20130101;
A61P 35/00 20180101; C07D 497/04 20130101; A61P 9/10 20180101; A61P
35/02 20180101; A61K 31/4162 20130101; A61P 19/02 20180101 |
Class at
Publication: |
514/253.04 ;
544/362; 544/371; 514/254.06; 548/360.5; 514/407; 546/199;
514/322 |
International
Class: |
A61K 31/496 20060101
A61K031/496; C07D 401/14 20060101 C07D401/14; C07D 401/12 20060101
C07D401/12; C07D 495/04 20060101 C07D495/04; A61K 31/4162 20060101
A61K031/4162; A61K 31/454 20060101 A61K031/454; A61P 35/00 20060101
A61P035/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 15, 2008 |
EP |
08156262.1 |
Claims
1. A compound of the formula (I): ##STR00037## wherein R represents
a straight or branched C.sub.1-C.sub.12 alkyl, an aryl or
heteroaryl group, R.sub.1 represents a hydrogen atom or a
substituent attached to any available atom of the A ring, R.sub.2
represents an optionally substituted group selected from straight
or branched C.sub.1-C.sub.6 alkyl, aryl, heteroaryl,
C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or alkynyl,
C.sub.3-C.sub.6 cycloalkyl C.sub.1-C.sub.6 alkyl, aryl
C.sub.1-C.sub.6 alkyl, heteroaryl C.sub.1-C.sub.6 alkyl, a 5 or 6
membered heterocyclyl and heterocyclyl C.sub.1-C.sub.6 alkyl with
from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur,
A ring represents a phenyl or a heterocycle and m is a value from 1
to 6, or a pharmaceutically acceptable salt thereof, for use as a
medicament.
2. A compound of formula (I) as defined in claim 1 for use as a
prodrug.
3. A compound of formula (I) according to claim 2, characterized it
is for use as prodrug for treating cell proliferative disorders
caused by and/or associated with an altered protein kinase
activity.
4. A compound of formula (I) according to claim 3, characterized it
is for use as prodrug for treating cancer.
5. A compound of the formula (I) as defined in claim characterized
in that R does not represent an usubstituted ethyl group.
6. A pharmaceutical composition comprising a compound of formula
(I) as defined in claim 1 or a pharmaceutically acceptable salt
thereof in association with a pharmaceutically acceptable
excipient.
7. A therapeutic method of treatment using as prodrug a compound of
the formula (I) as defined in claim 1.
8. A method for treating cell proliferative disorders caused by
and/or associated with an altered protein kinase activity, which
comprises administering to a mammal in need thereof an effective
amount of a compound of formula (I) as defined in claim 1 or a
pharmaceutical composition as specified herein.
9. A method according to claim 8, characterized in that the cell
proliferative disorder is cancer.
10. A compound of the formula: ##STR00038## or a pharmaceutically
acceptable salt thereof for use as a medicament.
11. A compound as defined in claim 10 for use as a prodrug.
12. A compound according to claim 11, characterized it is for use
as prodrug for treating cell proliferative disorders caused by
and/or associated with an altered protein kinase activity.
13. A compound according to claim 12, characterized it is for use
as prodrug for treating cancer.
14. A compound selected from the group consisting of: A01
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid methyl
ester; A02
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoy-
lamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
ethyl ester; A03
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid vinyl
ester; A04 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid propyl ester; A05
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; A06
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid allyl
ester; A07
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoy-
lamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propargyl ester; A08
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; A09 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid isobutyl ester; A010
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
sec-butyl ester; A011
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
tert-butyl ester; A012
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid pentyl
ester; A013
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzo-
ylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
neopentyl ester; A014
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid hexyl
ester; A015 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid heptyl ester; A016
5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid benzyl ester; A017
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid phenyl
ester; A018
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzo-
ylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; A019
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
cyclopentyl ester; A020
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; A021
5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester; A022
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; A023
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
methyl ester; A024
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; A025
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-ben-
zoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
vinyl ester; A026
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propyl ester; A027
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; A028
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid allyl
ester; A029
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-ben-
zoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propargyl ester; A030
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; A031
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-ben-
zoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
sec-butyl ester; A032
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; A033
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
tert-butyl ester; A034
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
pentyl ester; A035
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
neopentyl ester; A036
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid hexyl
ester; A037
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-ben-
zoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
heptyl ester; A038
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
benzyl ester; A039
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
phenyl ester; A040
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
cyclopentyl ester; A041
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; A042
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; A043
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; A044
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; B01
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid methyl ester;
B02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
B03
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid vinyl ester;
B04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propyl ester;
B05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl
ester; B06
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid allyl ester;
B07
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propargyl
ester; B08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester;
B09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl
ester; B010
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid sec-butyl
ester; B011
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid tert-butyl
ester; B012
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid pentyl
ester; B013
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid neopentyl
ester; B014
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid hexyl
ester; B015
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid heptyl
ester; B016
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid benzyl
ester; B017
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid phenyl
ester; B018
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; B019
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; B020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; B021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; B022
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; B023
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid methyl ester; B024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester; B025
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid vinyl ester; B026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propyl ester; B027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl ester; B028
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid allyl ester; B029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propargyl ester; B030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester; B031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl ester; B032
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid sec-butyl ester; B033
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid tert-butyl ester; B034
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid pentyl ester; B035
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid neopentyl ester; B036
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid hexyl ester; B037
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid heptyl ester; B038
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid benzyl ester; B039
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid phenyl ester; B040
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid cyclopentyl ester; B041
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester;
B042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; B043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
B044
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-chloroethyl ester;
B045
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
methyl ester; B046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
ethyl ester; B047
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
vinyl ester; B048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; B049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; B050
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
allyl ester; B051
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propargyl ester; B052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
butyl ester; B053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; B054
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
sec-butyl ester; B055
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
tert-butyl ester; B056
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
pentyl ester; B057 5-(1-Methyl-1-phenyl-ethyl
carbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbonyl)-amino]-benzoylamino}-f-
uro[3,2-c]pyrazole-1-carboxylic acid neopentyl ester; B058
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
hexyl ester; B059
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
heptyl ester; B060
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
benzyl ester; B061
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
phenyl ester; B062
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; B063
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; B064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; B065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; B066
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; B067
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
methyl ester; B068
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid ethyl
ester; B069
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-ca-
rbonyl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
vinyl ester; B070
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; B071
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; B072
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid allyl
ester; B073
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-ca-
rbonyl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propargyl ester; B074
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid butyl
ester; B075
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-ca-
rbonyl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; B076
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
sec-butyl ester; B077
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
tert-butyl ester; B078
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
pentyl ester; B079
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
neopentyl ester; B080
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid hexyl
ester; B081
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-ca-
rbonyl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
heptyl ester; B082
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
benzyl ester; B083
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
phenyl ester; B084
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; B085
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; B086
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; B087
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; B088
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C01
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; C02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; C03
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; C04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; C05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; C06
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester; C07
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propargyl ester; C08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; C09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; C010
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester; C011
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl ester; C012
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; C013
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester; C014
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester; C015
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester; C016
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester; C017
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester; C018
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl ester; C019
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester;
C020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroyethyl ester;
C022
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl ester;
C023
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; C024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; C025
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; C026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; C027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid allyl ester; C028
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propargyl ester; C029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; C030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; C031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; C032
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester; C033
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl ester; C034
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; C035
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester; C036
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester; C037
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester; C038
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester; C039
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester; C040
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester; C041
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl ester; C042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester; C044
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl ester; C045
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; C046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
C047
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester;
C048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; C049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; C050
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid allyl
ester; C051
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; C052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
C053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl
ester; C054
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; C055
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; C056
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; C057
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; C058
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
C059
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; C060
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; C061
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester; C062
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; C063
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; C064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; C066
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C067
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; C068
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; C069
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; C070
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; C071
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester;
C072
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester; C073
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propargyl ester;
C074
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; C075
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; C076
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester;
C077
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl ester;
C078
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; C079
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester;
C080
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester; C081
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester; C082
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester; C083
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester; C084
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl ester;
C085
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; C086
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C087
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
C088
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl ester;
C089
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; C090
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
C091
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester;
C092
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; C093
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; C094
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; C095
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
C096
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
C097
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl
ester; C098
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; C099
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; C0100
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; C0101
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; C0102
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
C0103
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; C0104
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; C0105
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester; C0106
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; C0107
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; C0108
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C0109
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; C0110
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C0111
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; C0112
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
C0113
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester;
C0114
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; C0115
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; C0116
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl
ester; C0117
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; C0118
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
C0119
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl
ester; C0120
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; C0121
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; C0122
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; C0123
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; C0124
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
C0125
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; C0126
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; C0127
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester; C0128
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; C0129
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; C0130
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C0131
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; C0132
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C0133
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
methyl ester; C0134
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
ethyl ester; C0135
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
vinyl ester; C0136
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propyl ester; C0137
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isopropyl ester; C0138
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
allyl ester; C0139
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; C0140
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
butyl ester; C0141
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; C0142
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; C0143
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
tert-butyl ester; C0144
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
pentyl ester; C0145
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; C0146
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
hexyl ester; C0147
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
heptyl ester; C0148
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
benzyl ester; C0149
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
phenyl ester; C0150
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; C0151
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
cyclopentyl ester; C0152
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C0153
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; C0154
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C0155
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid methyl ester;
C0156
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
C0157
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid vinyl ester;
C0158
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propyl ester;
C0159
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isopropyl ester;
C0160
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid allyl ester;
C0161
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propargyl ester;
C0162
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid butyl ester;
C0163
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isobutyl ester;
C0164
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid sec-butyl ester;
C0165
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid tert-butyl
ester; C0166
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid pentyl
ester; C0167
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid neopentyl
ester; C0168
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid hexyl
ester; C0169
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid heptyl
ester; C0170
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid benzyl
ester; C0171
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid phenyl
ester; C0172
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; C0173
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; C0174
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C0175
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; C0176
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; C0177
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; C0178
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
C0179
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester;
C0180
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; C0181
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; C0182
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid allyl
ester; C0183
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; C0184
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
C0185
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl
ester; C0186
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; C0187
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; C0188
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; C0189
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; C0190
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
C0191
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; C0192
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; C0193
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; C0194
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; C0195
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; C0196
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; C0197
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; C0198
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; D01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid methyl ester; D02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid ethyl ester; D03
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-methoxy-ethyl ester; D04
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-ethoxy-ethyl ester; D05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; D06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid methyl ester; D07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D08
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; D011
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid methyl ester; D012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D013
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D014
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D015
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; D016
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(te-
trahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; D017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ethyl ester; D018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid propyl ester; D019
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ispropyl ester; D020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid methyl ester; D021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid ethyl ester; D022
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid 2-methoxy-ethyl ester; D023
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid 2-ethoxy-ethyl ester; D024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid methyl ester; D025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid ethyl ester; D026
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid propyl ester; D027
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid isopropyl ester; D028
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid methyl ester; D029
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid ethyl ester; D030
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-methoxy-ethyl ester; D031
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-ethoxy-ethyl ester; D032
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; D033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid methyl ester; D034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid ethyl ester; D035
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester;
D038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid methyl ester; D039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid ethyl ester; D040
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D041
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D042
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester;
D043
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid methyl ester; D044
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid ethyl ester; D045
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid propyl ester; D046
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid ispropyl ester; D047
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid methyl ester; D048
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid ethyl ester; D049
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid 2-methoxy-ethyl ester; D050
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid 2-ethoxy-ethyl ester; D051
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid methyl ester; D052
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid ethyl ester; D053
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid propyl ester; D054
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid isopropyl ester; D055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; D056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; D057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D058
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D059
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; D060
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; D061
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D062
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
D063
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D064
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; D065
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-me-
thyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrah-
ydro-pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; D066
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D067
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
D068
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester;
D069
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; D070
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; D071
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; D072
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid propyl ester; D073
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ispropyl ester; D074
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; D075
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; D076
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D077
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D078
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; D079
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; D080
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid propyl ester; D081
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid isopropyl ester; D082
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; D083
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; D084
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D085
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D086
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; D087
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; D088
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D089
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
D090
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D091
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; D092
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-me-
thyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrah-
ydro-pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; D093
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; D094
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
D095
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester;
D096
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; D097
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; D098
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; D099
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid propyl ester; D0100
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ispropyl ester; D0101
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; D0102
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; D0103
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; D0104
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; D0105
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; D0106
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; D0107
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid propyl ester; D0108
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid isopropyl ester; E01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E03
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E04
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; E05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetr-
ahydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E08
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; E011
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(te-
trahydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E013
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E014
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; E015
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(te-
trahydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E016
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tet-
rahydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E019
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E022
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E023
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; E024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
E026
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E027
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E028
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E029
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; E030
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E031
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E032
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; E034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E035
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; E037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
E038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E040
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; E041
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E042
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E043
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; E044
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E045
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E046
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E047
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E048
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E049
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E050
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E051
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E052
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E053
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E054
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E058
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E059
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E060
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; E061
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E062
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E063
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; E064
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E065
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E066
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E067
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E068
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E069
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E070
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E071
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E072
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E073
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E074
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E075
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; E076
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; E077
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; E078
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; E079
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester and E080
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester, for use as medicament.
15. A compound of claim 14, with the exclusion of compounds coded
A02, A024 and C024, or a pharmaceutically acceptable salt thereof.
Description
[0001] The present invention relates to carbamoyl derivatives of
bicyclic carbonylamino-pyrazoles for use as medicament, in
particular for the treatment of diseases due to the malfunctioning
of protein kinases (PKs), such cancer and tumors, to the
pharmaceutical compositions comprising such carbamoyl derivatives,
and to their use as prodrugs of therapeutically active agents.
[0002] The present invention also relates to a method of treating
cancer and cell proliferation disorders using such prodrugs, and to
some new carbamoyl derivatives.
[0003] The malfunctioning of protein kinases (PKs) is the hallmark
of numerous diseases.
[0004] A large share of the oncogenes and proto-oncogenes involved
in human cancers code for PKs. The enhanced activities of PKs are
also implicated in many non-malignant diseases, such as benign
prostate hyperplasia, familial adenomatosis, polyposis,
neuro-fibromatosis, psoriasis, vascular smooth cell proliferation
associated with atherosclerosis, pulmonary fibrosis, arthritis
glomerulonephritis and post-surgical stenosis and restenosis.
[0005] PKs are also implicated in inflammatory conditions and in
the multiplication of viruses and parasites. PKs may also play a
major role in the pathogenesis and development of neurodegenerative
disorders.
[0006] For a general reference to PKs malfunctioning or
disregulation see, for instance, Current Opinion in Chemical
Biology 1999, 3, 459-465.
[0007] Among the several protein kinases known in the art as being
implicated in the growth of cancer cells are Aurora kinases, in
particular Aurora-2.
[0008] Aurora-2 was found to be over-expressed in a number of
different tumor types. Its gene locus maps at 20q13, a chromosomal
region frequently amplified in many cancers, including breast
[Cancer Res. 1999, 59(9), 2041-4] and colon.
[0009] 20q13 amplification correlates with poor prognosis in
patients with node-negative breast cancer and increased Aurora-2
expression is indicative of poor prognosis and decreased survival
time in bladder cancer patients [J. Natl. Cancer Inst., 2002,
94(17), 1320-9]. For a general reference to Aurora-2 role in the
abnormal centrosome function in cancer see also Molecular Cancer
Therapeutics, 2003, 2, 589-595.
[0010] The insulin-like growth factor 1 receptor (IGF-1R, IGF1R) is
a member of the insulin receptor subfamily of RTKs.
[0011] There exist several lines of evidence suggesting that IGF-1R
signaling can contribute to tumour genesis, and that interfering
with IGF-1R function represents a valid therapeutic option in
cancer. Forced expression of the receptor leads to ligand-dependent
transformed growth of murine and of rat fibroblasts (e.g. Kaleko
M., Rutter W. J. and Miller A. D. Mol Cell Biol vol. 10, pages
464-73, 1990; Rubini M., Hongo A., D'Ambrosio C. and Baserga R. Exp
Cell Res vol. 230, pages 284-92, 1997), and such transformed cells
are able to form tumors in vivo, with both in vitro transformation
and tumor formation in vivo being dependent upon an active kinase
domain (reviewed in Blakesley V. A., Stannard B. S., Kalebic T.,
Helman L. J., and LeRoith D. J Endocrinol. vol. 152, pages 339-44,
1997).
[0012] Compounds that are claimed having protein kinases inhibition
activity for use in treating numerous diseases due to the
malfunctioning of protein kinases are disclosed for example in WO
02/12242 (Various fused Pyrazoles); WO 03/028720, WO 08/074,749 and
WO 09/013,126 (Aminoindazoles); WO 04/056827, WO 05/005427,
WO2008017465 and WO2008043745 (Pyrrolo-pyrazoles); WO 04/007504, WO
04/013146, WO 05/074922, WO 07/009,898, WO07/138,017 and EP 2058315
(Furo- and Thieno-pyrazoles); WO 07/099,171, WO 07/068,637, WO
07/99166 and WO 07/068,619 (Arylsulfo-pyrrolo-pyrazoles and
arylsulfo-pyrrolo-pyridines).
[0013] Such patent applications also disclose processes for
preparing the claimed compounds, which processes can comprise
intermediates characterized from an ethoxycarbonyl group on one of
the nitrogen atoms present in the pyrazole ring.
[0014] All the patents, patent applications and scientific
publications cited in the present disclosure are incorporated
herein by references.
[0015] The administration and therapeutic effectiveness of such
compounds having protein kinases inhibition could be limited,
however, for example for low or absence of oral bioavailability,
low water solubility or stability.
[0016] Moreover, since these chemotherapeutic agents can be
cytotoxic to normal tissues, the use of prodrugs is beneficial in
terms of reduction of the side-effects.
[0017] A large amount of prodrug strategies are known, based on
various modifications of the parent drug, but none of them teaches
or suggests the specific prodrugs of the present inventions.
[0018] On the contrary, the above noted patent applications
describe some carbamoyl derivatives as useful intermediates for the
chemical preparation of the desired final active drugs. The
identification of the new use is therefore completely
unexpected.
[0019] It is an object of the invention to provide a compound of
the formula (I) for use as medicament, preferably as prodrug,
useful in therapy as agent against a host of diseases caused by
and/or associated to a disregulated protein kinase activity, that
is for the treatment of diseases due to the malfunctioning of
protein kinases (PKs), such cancer or tumors.
[0020] More specifically, the prodrugs of this invention are useful
in the treatment of a variety of cancers including, but not limited
to: carcinoma such as bladder, breast, colon, kidney, liver, lung,
including small cell lung cancer, esophagus, gall-bladder, ovary,
pancreas, stomach, cervix, thyroid, prostate, and skin, including
squamous cell carcinoma; hematopoietic tumors of lymphoid lineage,
including leukemia, acute lymphocytic leukemia, acute lymphoblastic
leukemia, B-cell lymphoma, T-cell-lymphoma, Hodgkin's lymphoma,
non-Hodgkin's lymphoma, hairy cell lymphoma and Burkett's lymphoma;
hematopoietic tumors of myeloid lineage, including acute and
chronic myelogenous leukemias, myelodysplastic syndrome and
promyelocytic leukemia; tumors of mesenchymal origin, including
fibrosarcoma and rhabdomyosarcoma; tumors of the central and
peripheral nervous system, including astrocytoma, neuroblastoma,
glioma and schwannomas; other tumors, including melanoma, seminoma,
teratocarcinoma, osteosarcoma, xeroderma pigmentosum,
keratoxanthoma, thyroid follicular cancer and Kaposi's sarcoma.
[0021] Due to the key role of PKs in the regulation of cellular
proliferation, these prodrugs are also useful in the treatment of a
variety of cell proliferative disorders such as, for instance,
benign prostate hyperplasia, familial adenomatosis, polyposis,
neuro-fibromatosis, psoriasis, vascular smooth cell proliferation
associated with atherosclerosis, pulmonary fibrosis, arthritis
glomerulonephritis and post-surgical stenosis and restenosis.
[0022] Accordingly, in a first embodiment, the present invention
provides a compound of the formula (I):
##STR00002##
wherein R represents a straight or branched C.sub.1-C.sub.12 alkyl,
an aryl or heteroaryl group, R.sub.1 represents a hydrogen atom or
a substituent attached to any available atom of the A ring, R.sub.2
represents an optionally substituted group selected from straight
or branched C.sub.1-C.sub.6 alkyl, aryl, heteroaryl,
C.sub.3-C.sub.6 cycloalkyl, C.sub.2-C.sub.6 alkenyl or alkynyl,
C.sub.3-C.sub.6 cycloalkyl C.sub.1-C.sub.6 alkyl, aryl
C.sub.1-C.sub.6 alkyl, heteroaryl C.sub.1-C.sub.6 alkyl, a 5 or 6
membered heterocyclyl and heterocyclyl C.sub.1-C.sub.6 alkyl with
from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulphur,
A ring represents a phenyl or a heterocycle and m is a value from 1
to 6, or a pharmaceutically acceptable salt thereof, for use as a
medicament.
[0023] More preferably, the present invention provide a compound of
formula (I) as defined above for use as a prodrug. Even more
preferably, the invention provides a compound of formula (I) as
above defined for use as prodrug for treating cell proliferative
disorders caused by and/or associated with an altered protein
kinase activity, in particular cancer.
[0024] The invention further provides any therapeutic method of
treatment using as prodrug a compound of the formula (I) as defined
above.
[0025] It is still a further object of the present invention a
compound of the formula (I) as defined above characterized in that
R does not represent an usubstituted ethyl group.
[0026] The present invention also provides a method for treating
cell proliferative disorders caused by and/or associated with an
altered protein kinase activity, which comprises administering to a
mammal in need thereof an effective amount of a compound of formula
(I) as above defined.
[0027] The above method enables treatment of cell proliferative
disorders caused by and/or associated with altered protein kinases,
for example Aurora kinases or IGF-1R activity.
[0028] In a preferred embodiment of the method described above, the
cell proliferative disorder is cancer.
[0029] Specific types of cancer that may be treated include
carcinoma, squamous cell carcinoma, hematopoietic tumors of myeloid
or lymphoid lineage, tumors of mesenchymal origin, tumors of the
central and peripheral nervous system, melanoma, seminoma,
teratocarcinoma, osteosarcoma, xeroderma pigmentosum,
keratoxanthoma, thyroid follicular cancer, and Kaposi's
sarcoma.
[0030] The present invention also includes pharmaceutical
compositions comprising a compound of formula (I) as defined above
or a pharmaceutically acceptable salt thereof in association with a
pharmaceutically acceptable excipient, which may be a carrier or a
diluent, and to a method for treating cell proliferative disorders
caused by and/or associated with an altered protein kinase
activity, which comprises administering to a mammal in need thereof
an effective amount of a compound of formula (I) as above defined
or a pharmaceutical composition as specified herein. A more
complete appreciation of the invention and many of the attendant
advantages thereof will be readily obtained as the same becomes
better understood by reference to the following detailed
description.
[0031] The compounds of formula (I) may have asymmetric carbons and
may therefore exist either as racemic admixtures or as individual
optical isomers.
[0032] Accordingly, all the possible isomers and their admixtures
are also within the scope of the present invention.
[0033] In addition to the above, as will be readily appreciated,
the compounds of formula (I) may exist as isomers or mixtures
thereof of the formulas (Ia) and (Ib):
##STR00003##
[0034] The two isomers of formula (Ia) and (Ib) may be conveniently
separated according to well-known methods, for instance under
chromatographic conditions, and each isomer so isolated
subsequently worked out. In the alternative, the mixture of isomers
can be treated as such in the subsequent steps of the process,
without providing any separation.
[0035] The above process can be carried out according to methods
well known in the art.
[0036] From all of the above, it is clear to the person skilled in
the art that if a compound of formula (I), prepared according to
the above process, is obtained as a mixture of isomers, their
separation into the single isomers of formula (I), carried out
according to conventional techniques, is still within the scope of
the present invention.
[0037] Likewise, the conversion into the free compound (I) of a
corresponding salt thereof, according to well-known methods, is
still within the scope of the invention.
[0038] As used herein, unless otherwise specified, with the term
straight or branched C.sub.1-C.sub.12 or C.sub.1-C.sub.6 alkyl,
either as such or as aryl C.sub.1-C.sub.6 alkyl or heteroaryl
C.sub.1-C.sub.6 alkyl, we intend a group such as, for instance
methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, sec-butyl,
n-pentyl, n-hexyl, n-heptyl, and the like. Preferably, it is a
C.sub.1-C.sub.4 alkyl, e.g. methyl, ethyl, n-propyl, isopropyl,
n-butyl, t-butyl, sec-butyl.
[0039] With the term aryl group we intend any aromatic carbocyclic
ring system of 1 or 2 ring moieties, either fused or linked to each
other through a single bond, for instance including phenyl, - or
-naphthyl or biphenyl groups.
[0040] With the term heteroaryl we intend any aromatic heterocyclic
ring which may comprise an optionally benzocondensed 5 or 6
membered heterocycle with from 1 to 3 heteroatoms selected among N,
O or S.
[0041] Non limiting examples of heteroaryl groups according to the
invention may thus include, for instance, pyridyl, pyrazinyl,
pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl,
isothiazolyl, pyrrolyl, phenyl-pyrrolyl, furyl, phenyl-furyl,
oxazolyl, isoxazolyl, pyrazolyl, thienyl, benzothienyl,
isoindolinyl, benzoimidazolyl, quinolinyl, isoquinolinyl,
1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, and the like.
[0042] With the term halogen atom we intend a fluorine, chlorine,
bromine or iodine atom.
[0043] With the term C.sub.3-C.sub.6 cycloalkyl we intend any group
such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. With
the term C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl group
we intend any unsaturated straight or branched group such as, for
instance, vinyl, allyl, 1-propenyl, isopropenyl, 1-, 2- or
3-butenyl, pentenyl, hexenyl, ethynyl, 1- or 2-propynyl, butynyl,
pentynyl, hexynyl, and the like.
[0044] With the term heterocycle, heterocyclyl or heterocyclic
group we also intend an optionally benzocondensed 4 to 7 membered
heterocycle, hence encompassing aromatic heterocyclic groups also
known as heteroaryl groups, either saturated or partially
unsaturated, with from 1 to 3 heteroatoms selected among N, O and
S.
[0045] Examples of these 4 or 7 membered heterocyclic groups are,
for instance, 1,3-dioxolane, pyran, pyrrolidine, pyrroline,
imidazoline, imidazolidine, pyrazolidine, pyrazoline, piperidine,
piperazine, morpholine, tetrahydrofuran, hexamethyleneimine,
1,4-hexahydrodiazepine, azetidine, and the like.
[0046] According to the present invention, A ring in formula (I)
above represents a phenyl or a heterocycle such as
##STR00004##
wherein n R.sub.1 and m are as defined above.
[0047] When R.sub.1 represents a substituent attached to any
available atom of the A ring, it is selected from: halogen, nitro,
oxo groups (.dbd.O), carboxy, cyano, alkyl, polyfluorinated alkyl,
alkenyl, alkynyl, cycloalkyl, cycloalkenyl; aryl, heterocyclyl,
alkyl-heterocyclyl, heterocyclyl-alkyl, amino groups and
derivatives thereof such as, for instance, alkylamino,
dialkylamino, arylamino, diarylamino, ureido, alkylureido or
arylureido; carbonylamino groups and derivatives thereof such as,
for instance, formylamino, alkylcarbonylamino,
alkenylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino;
hydroxy groups and derivatives thereof such as, for instance,
alkoxy, polyfluorinated alkoxy, aryloxy, heterocylyloxy,
alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy or
alkylideneaminoxy; carbonyl groups and derivatives thereof such as,
for instance, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl,
aryloxycarbonyl, cycloalkyloxycarbonyl, aminocarbonyl,
alkylaminocarbonyl, dialkylaminocarbonyl; sulfurated derivatives
such as, for instance, alkylthio, arylthio, alkylsulfonyl,
arylsulfonyl, alkylsulfinyl, arylsulfinyl, arylsulfonyloxy,
aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl.
[0048] Needless to say, when m is neither one nor zero, the two or
more substituents that R.sub.1 represents may be the same, such as
two methyl groups, or have different meanings, for example halogen
atom and alkyl, on the same atom or on two or more different atoms
of the A ring.
[0049] In their turn, whenever appropriate, each of the above
substituents may be further substituted by one or more of the
aforementioned groups.
[0050] According to the meanings provided to the groups R and
R.sub.2, any of the groups in their definitions above may be
optionally further substituted in any of their free positions by
one or more groups, for instance 1 to 6 groups, such substituents
being as defined above for R.sub.1.
[0051] The term "pharmaceutically acceptable salts" embraces salts
commonly used to form alkali metal salts and to form addition salts
of free acids or free bases. The nature of the salt is not
critical, provided that it is pharmaceutically acceptable. Suitable
pharmaceutically acceptable acid addition salts of the compounds of
the present invention may be prepared from an inorganic or organic
acid. Examples of such inorganic acids are hydrochloric,
hydrobromic, hydroiodic, nitric, carbonic, sulfuric, and phosphoric
acid. Appropriate organic acids may be selected from aliphatic,
cycloaliphatic, aromatic, arylaliphatic, heterocyclic, carboxylic
and sulfonic classes of organic acids, examples of which are
formic, acetic, trifluoroacetic, propionic, succinic, glycolic,
gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic,
maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic,
mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic,
embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic,
pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic,
stearic, cyclohexylaminosulfonic, algenic, hydroxybutyric,
galactaric and galacturonic acid. Suitable pharmaceutically
acceptable base addition salts of the compounds of the present
invention include metallic salts made from aluminum, calcium,
lithium, magnesium, potassium, sodium and zinc or organic salts
made from N,N'-dibenzylethylenediamine, chloroprocaine, choline,
diethanolamine, ethylenediamine, meglumine (N-methyl-glucamine) and
procaine. All of these salts may be prepared by conventional means
from the corresponding compounds of the present invention, for
instance by reacting them with the appropriate acid or base.
Preferably, the present invention provides a compound of formula
(I.sup.i), (I.sup.ii), (I.sub.iv), (I.sub.iv), (I.sub.v),
(I.sup.vi), (I.sup.vii) and
##STR00005##
(I.sup.viii): wherein m, R, R.sub.1 and R.sub.2 are as defined
above; for example when m is 2 or 3, the further R.sub.1
substituent(s) on the phenyl or heterocyclic ring represent(s) a
methyl, ethyl or cyclopropyl group.
[0052] In the displayed formulas in the present specification, a
dotted line crosses the bond that links the substituent to the main
framework of the molecula.
[0053] Preferably, R is a group selected from
##STR00006##
[0054] Preferably, for a compound of the formula (I.sup.i),
(I.sup.ii), (I.sub.iii), (I.sub.iv), (I.sub.v), (I.sup.vi), R.sub.1
is a group selected from:
##STR00007## ##STR00008## ##STR00009## ##STR00010##
and, more preferably, the above defined R.sub.1 substituent in a
compound of the formula (I.sup.iv), (I.sup.v) or (I.sup.vi) is on
the heteroatom.
[0055] Preferably, for a compound of the formula (I.sup.vii) or
(I.sup.viii), R.sub.1 is a group selected from:
##STR00011##
[0056] Lastly, preferably R.sub.2 is a group selected from:
##STR00012## ##STR00013## ##STR00014## ##STR00015## ##STR00016##
##STR00017## ##STR00018## ##STR00019## ##STR00020## ##STR00021##
##STR00022##
[0057] In another preferred aspect, the present invention provides
a compound of formula (I.sup.iv'):
##STR00023##
wherein R is as defined above, or a pharmaceutically acceptable
salt thereof, for use as a medicament; more preferably as prodrug,
even more preferably as anticancer produg.
[0058] Preferably, the configuration of the asymmetric carbon atom
is (R), and R is selected from methyl, ethyl, cyclopentyl,
n-pentyl, t-butyl, 2-propynyl, allyl, benzyl, n-heptyl, neopentyl,
n-butyl, iso-butyl, vinyl, 3-chloro-propyl, 3-fluoro-propyl,
2-methoxyethyl, 2-ethoxyethyl, iso-propyl, n-propyl, phenyl,
n-hexyl, sec-butyl, isopropenyl or a group of formula:
##STR00024##
[0059] More preferably, the present invention provides a compound
of formula (r) having (R) configuration and characterized in that R
is a ethyl group for use as a medicament; more preferably as
prodrug, even more preferably as anticancer produg.
[0060] Even more preferably, the present invention provides the
compound of the formula:
##STR00025##
or a pharmaceutically acceptable salt thereof for use as a
medicament, preferably as prodrug, even more preferably as prodrug
for treating cell proliferative disorders caused by and/or
associated with an altered protein kinase activity, in particular
as prodrug for treating cancer.
[0061] Such compound is coded A024 herein below.
[0062] The invention further provides any therapeutic method of
treatment using as prodrug the compound coded A024 as defined
above.
[0063] The present invention also includes pharmaceutical
compositions comprising a compound coded A024 as defined above or a
pharmaceutically acceptable salt thereof in association with a
pharmaceutically acceptable excipient, which may be a carrier or a
diluent, and to a method for treating cell proliferative disorders
caused by and/or associated with an altered protein kinase
activity, which comprises administering to a mammal in need thereof
an effective amount of a compound coded A24 as defined above or a
pharmaceutical composition as specified herein.
[0064] In another aspect, there is provided a compound of formula
(I.sup.iv) wherein R is a straight or branched C.sub.1-C.sub.12
alkyl, an aryl or heteroaryl group, but not an ethyl group.
[0065] Specific, non limiting, examples of compounds of the
invention, whenever appropriate in the form of pharmaceutically
acceptable salts, as such, for use as medicament or both, are the
following: [0066] A01
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid methyl
ester; [0067] A02
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0068] A03
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid vinyl
ester; [0069] A04
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid propyl
ester; [0070] A05
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0071] A06
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid allyl
ester; [0072] A07
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propargyl ester; [0073] A08
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0074] A09
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0075] A010 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid sec-butyl ester; [0076] A011
5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid tert-butyl ester; [0077]
A012
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid pentyl
ester; [0078] A013 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid neopentyl ester; [0079] A014
5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid hexyl ester; [0080] A015
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid heptyl
ester; [0081] A016 5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid benzyl ester; [0082] A017
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid phenyl
ester; [0083] A018
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0084] A019
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
cyclopentyl ester; [0085] A020
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0086] A021
5-(2,6-Diethyl-phenyl
carbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylamino]-5,6-dihydro-4H-py-
rrolo[3,4-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester; [0087]
A022
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0088] A023
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
methyl ester; [0089] A024
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0090] A025
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid vinyl
ester; [0091] A026
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propyl ester; [0092] A027
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0093] A028
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid allyl
ester; [0094] A029
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propargyl ester; [0095] A030
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0096] A031
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
sec-butyl ester; [0097] A032
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0098] A033
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
tert-butyl ester; [0099] A034
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
pentyl ester; [0100] A035
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
neopentyl ester; [0101] A036
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid hexyl
ester; [0102] A037
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
heptyl ester; [0103] A038
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
benzyl ester; [0104] A039
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
phenyl ester; [0105] A040
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
cyclopentyl ester; [0106] A041
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0107] A042
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0108] A043
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0109] A044
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0110] B01
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid methyl ester;
[0111] B02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid ethyl
ester; [0112] B03
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid vinyl ester;
[0113] B04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0114] B05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl
ester; [0115] B06
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid allyl ester;
[0116] B07
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propargyl
ester; [0117] B08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester;
[0118] B09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl
ester; [0119] B010
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid sec-butyl
ester; [0120] B011
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0121] B012
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid pentyl ester;
[0122] B013
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid neopentyl
ester; [0123] B014
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid hexyl ester;
[0124] B015
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid heptyl
ester; [0125] B016
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid benzyl ester;
[0126] B017
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid phenyl
ester; [0127] B018
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0128] B019
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; [0129] B020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0130] B021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; [0131] B022
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-chloroethyl
ester; [0132] B023
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid methyl ester; [0133]
B024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester; [0134] B025
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid vinyl ester; [0135] B026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propyl ester; [0136]
B027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl ester; [0137]
B028
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid allyl ester; [0138] B029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propargyl ester; [0139]
B030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester; [0140] B031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl ester; [0141]
B032
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid sec-butyl ester; [0142]
B033
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid tert-butyl ester; [0143]
B034
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid pentyl ester; [0144]
B035
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid neopentyl ester; [0145]
B036
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid hexyl ester; [0146] B037
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid heptyl ester; [0147]
B038
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid benzyl ester; [0148]
B039
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid phenyl ester; [0149]
B040
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid cyclopentyl ester;
[0150] B041
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester;
[0151] B042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benz-
oylamino)-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0152] B043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
[0153] B044
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benz-
oylamino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-chloroethyl
ester; [0154] B045
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
methyl ester; [0155] B046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
ethyl ester; [0156] B047
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
vinyl ester; [0157] B048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0158] B049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl
ester; [0159] B050
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
allyl ester; [0160] B051
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propargyl ester;
[0161] B052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
butyl ester; [0162] B053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; [0163] B054
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
sec-butyl ester; [0164] B055
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
tert-butyl ester; [0165] B056
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
pentyl ester; [0166] B057
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
neopentyl ester; [0167] B058
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
hexyl ester; [0168] B059
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
heptyl ester; [0169] B060
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
benzyl ester; [0170] B061
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
phenyl ester; [0171] B062
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; [0172] B063
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0173] B064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0174] B065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0175] B066
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0176] B067
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
methyl ester; [0177] B068
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid ethyl
ester; [0178] B069
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid vinyl
ester; [0179] B070
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0180] B071
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; [0181] B072
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid allyl
ester; [0182] B073
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propargyl ester; [0183] B074
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid butyl
ester; [0184] B075
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; [0185] B076
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
sec-butyl ester; [0186] B077
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
tert-butyl ester; [0187] B078
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
pentyl ester; [0188] B079
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
neopentyl ester; [0189] B080
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid hexyl
ester; [0190] B081
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
heptyl ester; [0191] B082
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
benzyl ester; [0192] B083
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
phenyl ester; [0193] B084
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0194] B085
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
cyclopentyl ester; [0195] B086
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0196] B087
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0197] B088
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0198] C01
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; [0199]
C02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0200] C03
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; [0201] C04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0202]
C05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0203]
C06
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester; [0204] C07
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propargyl ester; [0205]
C08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; [0206] C09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; [0207]
C010
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester; [0208]
C011
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl ester;
[0209] C012
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; [0210]
C013
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester; [0211]
C014
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester; [0212]
C015
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester; [0213]
C016
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester; [0214]
C017
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester; [0215]
C018
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl ester;
[0216] C019
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester;
[0217] C020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzo-
ylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0218] C021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroyethyl ester;
[0219] C022
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzo-
ylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl
ester; [0220] C023
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; [0221] C024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0222] C025
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; [0223] C026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0224] C027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid allyl ester; [0225] C028
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propargyl ester; [0226] C029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0227] C030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; [0228] C031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; [0229] C032
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester; [0230] C033
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl ester; [0231] C034
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; [0232] C035
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester; [0233] C036
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester; [0234] C037
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester; [0235] C038
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester; [0236] C039
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester; [0237] C040
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl ester; [0238]
C041
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl ester; [0239]
C042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0240] C043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester; [0241]
C044
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl ester; [0242]
C045
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; [0243] C046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0244] C047
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl
ester; [0245] C048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0246] C049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0247] C050
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
[0248] C051
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; [0249] C052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0250] C053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0251] C054
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl
ester; [0252] C055
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0253] C056
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; [0254] C057
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl
ester; [0255] C058
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
[0256] C059
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; [0257] C060
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; [0258] C061
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester;
[0259] C062
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0260] C063
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0261] C064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0262] C065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0263] C066
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0264] C067
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl ester; [0265]
C068
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0266]
C069
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl ester; [0267]
C070
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0268]
C071
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester;
[0269] C072
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
[0270] C073
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propargyl
ester; [0271] C074
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; [0272]
C075
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester;
[0273] C076
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl ester;
[0274] C077
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0275] C078
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl ester; [0276]
C079
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl ester;
[0277] C080
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
[0278] C081
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl ester;
[0279] C082
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl ester;
[0280] C083
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl ester;
[0281] C084
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0282] C085
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; [0283] C086
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0284] C087
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
[0285] C088
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-chloroethyl
ester; [0286] C089
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; [0287] C090
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0288] C091
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl
ester; [0289] C092
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0290] C093
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0291] C094
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propargyl
ester; [0292] C095
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
[0293] C096
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl
ester; [0294] C097
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl
ester; [0295] C098
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl
ester; [0296] C099
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0297] C0100
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; [0298] C0101
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl
ester; [0299] C0102
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
[0300] C0103
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; [0301] C0104
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; [0302] C0105
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester; [0303] C0106
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0304] C0107
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0305] C0108
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0306] C0109
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0307] C0110
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0308] C0111
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; [0309] C0112
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0310] C0113
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl
ester; [0311] C0114
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0312] C0115
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0313] C0116
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
[0314] C0117
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; [0315] C0118
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0316] C0119
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; [0317] C0120
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl
ester; [0318] C0121
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0319] C0122
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; [0320] C0123
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl
ester; [0321] C0124
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
[0322] C0125
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; [0323] C0126
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; [0324] C0127
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid phenyl
ester; [0325] C0128
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0326] C0129
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0327] C0130
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0328] C0131
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0329] C0132
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0330] C0133
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
methyl ester; [0331] C0134
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
ethyl ester; [0332] C0135
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
vinyl ester; [0333] C0136
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propyl ester; [0334] C0137
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isopropyl ester; [0335] C0138
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
allyl ester; [0336] C0139
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; [0337] C0140
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
butyl ester; [0338] C0141
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0339] C0142
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
sec-butyl ester; [0340] C0143
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
tert-butyl ester; [0341] C0144
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
pentyl ester; [0342] C0145
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
neopentyl ester; [0343] C0146
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
hexyl ester; [0344] C0147
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
heptyl ester; [0345] C0148
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
benzyl ester; [0346] C0149
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
phenyl ester; [0347] C0150
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0348] C0151
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
cyclopentyl ester; [0349] C0152
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0350] C0153
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0351] C0154
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0352] C0155
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid methyl ester;
[0353] C0156
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid ethyl
ester;
[0354] C0157
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid vinyl ester;
[0355] C0158
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0356] C0159
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isopropyl ester;
[0357] C0160
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid allyl
ester; [0358] C0161
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propargyl ester;
[0359] C0162
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid butyl
ester; [0360] C0163
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isobutyl ester;
[0361] C0164
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid sec-butyl
ester; [0362] C0165
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0363] C0166
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid pentyl ester;
[0364] C0167
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid neopentyl
ester; [0365] C0168
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid hexyl ester;
[0366] C0169
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid heptyl
ester; [0367] C0170
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid benzyl ester;
[0368] C0171
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid phenyl
ester; [0369] C0172
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0370] C0173
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-methoxyethyl
ester; [0371] C0174
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0372] C0175
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; [0373] C0176
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-chloroethyl
ester; [0374] C0177
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid methyl
ester; [0375] C0178
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0376] C0179
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid vinyl
ester; [0377] C0180
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0378] C0181
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0379] C0182
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid allyl ester;
[0380] C0183
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
propargyl ester; [0381] C0184
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0382] C0185
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0383] C0186
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid sec-butyl
ester; [0384] C0187
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid tert-butyl
ester; [0385] C0188
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid pentyl
ester; [0386] C0189
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid neopentyl
ester; [0387] C0190
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid hexyl ester;
[0388] C0191
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; [0389] C0192
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid heptyl
ester; [0390] C0193
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid benzyl
ester; [0391] C0194
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid cyclopentyl
ester; [0392] C0195
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester; [0393] C0196
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0394] C0197
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0395] C0198
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-chloroethyl ester; [0396] D01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid methyl ester; [0397] D02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid ethyl ester; [0398] D03
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-methoxy-ethyl ester; [0399] D04
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-ethoxy-ethyl ester; [0400] D05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; [0401] D06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0402] D07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0403] D08
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0404]
D09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0405]
D010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; [0406] D011
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0407] D012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0408] D013
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0409]
D014
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0410]
D015
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester; [0411] D016
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid methyl ester; [0412] D017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ethyl ester; [0413] D018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid propyl ester; [0414] D019
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ispropyl ester; [0415] D020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid methyl ester; [0416] D021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid ethyl ester; [0417] D022
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid 2-methoxy-ethyl ester; [0418] D023
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid 2-ethoxy-ethyl ester; [0419] D024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid methyl ester; [0420] D025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid ethyl ester; [0421] D026
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid propyl ester; [0422] D027
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid isopropyl ester; [0423] D028
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid methyl ester; [0424] D029
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid ethyl ester; [0425] D030
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-methoxy-ethyl ester; [0426] D031
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-ethoxy-ethyl ester; [0427] D032
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; [0428] D033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid methyl ester; [0429] D034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid ethyl ester; [0430] D035
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0431] D036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0432] D037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester;
[0433] D038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-meth-
yl-amino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0434] D039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid ethyl ester; [0435] D040
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0436] D041
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0437] D042
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl
ester;
[0438] D043
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid methyl ester; [0439] D044
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid ethyl ester; [0440] D045
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid propyl ester; [0441] D046
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid ispropyl ester; [0442] D047
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid methyl ester; [0443] D048
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid ethyl ester; [0444] D049
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid 2-methoxy-ethyl ester; [0445] D050
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid 2-ethoxy-ethyl ester; [0446] D051
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid methyl ester; [0447] D052
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid ethyl ester; [0448] D053
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid propyl ester; [0449] D054
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid isopropyl ester; [0450] D055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0451] D056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0452] D057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0453] D058
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0454] D059
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester;
[0455] D060
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0456] D061
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0457] D062
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
[0458] D063
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-met-
hyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahy-
dro-pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester;
[0459] D064
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-met-
hyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahy-
dro-pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0460] D065
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0461] D066
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0462] D067
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
[0463] D068
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-me-
thyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrah-
ydro-pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl
ester; [0464] D069
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0465] D070
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; [0466] D071
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; [0467] D072
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid propyl ester; [0468] D073
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ispropyl ester; [0469] D074
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0470] D075
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0471] D076
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0472] D077
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0473] D078
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0474] D079
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0475] D080
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid propyl ester; [0476] D081
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid isopropyl ester; [0477] D082
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0478] D083
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0479] D084
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0480] D085
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0481] D086
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester;
[0482] D087
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0483] D088
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0484] D089
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
[0485] D090
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-met-
hyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahy-
dro-pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester;
[0486] D091
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-met-
hyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahy-
dro-pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0487] D092
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0488] D093
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0489] D094
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester;
[0490] D095
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-me-
thyl-amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrah-
ydro-pyrazolo[4,3-c]pyridine-1-carboxylic acid 2-ethoxy-ethyl
ester; [0491] D096
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0492] D097
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; [0493] D098
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; [0494] D099
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid propyl ester; [0495] D0100
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ispropyl ester; [0496] D0101
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0497] D0102
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0498] D0103
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0499] D0104
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid 2-ethoxy-ethyl ester; [0500] D0105
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0501] D0106
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0502] D0107
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid propyl ester; [0503] D0108
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid isopropyl ester; [0504] E01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0505] E02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0506] E03
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0507] E04
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0508] E05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0509] E06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0510] E07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0511] E08
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0512] E09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester;
[0513] E010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0514] E011
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0515] E012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0516] E013
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0517] E014
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0518] E015
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0519] E016
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0520] E017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0521] E018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0522] E019
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0523] E020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0524] E021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0525] E022
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0526] E023
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0527] E024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0528] E025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0529] E026
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-m-
ethoxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0530] E027
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0531] E028
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0532] E029
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0533] E030
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0534] E031
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0535] E032
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0536] E033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0537] E034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0538] E035
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0539] E036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0540] E037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0541] E038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-m-
ethoxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0542] E039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0543] E040
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0544] E041
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0545] E042
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0546] E043
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0547] E044
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0548] E045
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0549] E046
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0550] E047
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0551] E048
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0552] E049
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0553] E050
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0554] E051
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0555] E052
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0556] E053
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0557] E054
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0558] E055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0559] E056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0560] E057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0561] E058
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0562] E059
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0563] E060
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0564] E061
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0565] E062
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0566] E063
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0567] E064
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0568] E065
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0569] E066
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0570] E067
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0571] E068
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0572] E069
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0573] E070
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0574] E071
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0575] E072
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0576] E073
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0577] E074
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0578] E075
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester; [0579] E076
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0580] E077
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0581] E078
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0582] E079
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-ethoxy-ethyl ester and [0583] E080
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester.
[0584] As stated, the compounds listed above "per se" are another
object of the present invention as such their pharmaceutically
acceptable salts, but for the compounds coded A02, A024 and C024,
known as intermediates, that are object of the present invention
for use as medicament as above described only.
[0585] Even more preferred compound of the present invention are
the following ones: [0586] A02
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0587] A04
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid propyl
ester; [0588] A05
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0589] A08
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0590] A09
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0591] A020
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0592] A021
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0593] A024
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0594] A026
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propyl ester; [0595] A027
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0596] A030
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0597] A032
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0598] A042
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0599] A043
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0600] B02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
[0601] B04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0602] B05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl
ester; [0603] B08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester;
[0604] B09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl
ester; [0605] B020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0606] B021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; [0607] B024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester; [0608] B026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propyl ester; [0609]
B027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl ester; [0610]
B030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid butyl ester; [0611] B031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isobutyl ester; [0612]
B042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0613] B043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
[0614] B046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-c-
arbonyl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
ethyl ester; [0615] B048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0616] B049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; [0617] B052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
butyl ester; [0618] B053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; [0619] B064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0620] B065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0621] B068
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid ethyl
ester; [0622] B070
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0623] B071
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; [0624] B074 5-(1-Methyl-1-phenyl-ethyl
carbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbonyl)-amino]-benzoylamino}-fu-
ro[3,2-c]pyrazole-1-carboxylic acid butyl ester; [0625] B075
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isobutyl ester; [0626] B086
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0627] B087
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0628] C02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0629] C04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0630]
C05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0631]
C08
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; [0632] C09
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; [0633]
C20
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0634] C21
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroyethyl ester;
[0635] C024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamin-
o)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0636] C026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0637] C029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0638] C030
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid butyl ester; [0639] C031
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester; [0640] C042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0641] C043
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester; [0642]
C046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0643] C048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0644] C049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0645] C052
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0646] C053
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0647] C064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0648] C065
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0649] C068
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0650]
C070
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0651]
C071
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester;
[0652] C074
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0653] C075
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isobutyl ester;
[0654] C086
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethy-
lcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0655] C087
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid 2-fluoroethyl ester;
[0656] C090
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl
ester; [0657] C092
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0658] C093
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0659] C096
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0660] C097
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0661] C0108
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0662] C0109
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0663] C0112
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0664] C0114
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0665] C0115
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0666] C0118
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0667] C0120
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0668] C0130
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0669] C0131
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0670] C0134
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
ethyl ester; [0671] C0136
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propyl ester; [0672] C0137
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isopropyl ester; [0673] C0140
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
butyl ester; [0674] C0141
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0675] C0152
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0676] C0153
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0677] C0156
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
[0678] C0158
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0679] C0159
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isopropyl
ester;
[0680] C0162
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid butyl ester;
[0681] C0163
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isobutyl
ester; [0682] C0174
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0683] C0175
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; [0684] C0178
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0685] C0180
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0686] C0181
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0687] C0184
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid butyl ester;
[0688] C0185
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
isobutyl ester; [0689]
C0196-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-am-
ino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0690] C0197
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0691] D01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid methyl ester;
[0692] D02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-
-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[-
4,3-c]pyridine-1-carboxylic acid ethyl ester; [0693] D03
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-methoxy-ethyl ester; [0694] D04
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-ethoxy-ethyl ester; [0695] D05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid 2-(2-methoxy-ethoxy)-ethyl ester; [0696] D06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0697] D07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyp-methyl-amin-
o]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazol-
o[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0698] D011
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0699] D012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0700] D016
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid methyl ester; [0701] D017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ethyl ester; [0702] D018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid propyl ester; [0703] D020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid methyl ester; [0704] D021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid ethyl ester; [0705] D024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid methyl ester; [0706] D025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid ethyl ester; [0707] D028
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid methyl ester; [0708] D029
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid ethyl ester; [0709] D030
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-meth-
oxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid 2-methoxy-ethyl ester; [0710] D033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid methyl ester; [0711] D034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid ethyl ester; [0712] D038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid methyl ester; [0713] D039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid ethyl ester; [0714] D043
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid methyl ester; [0715] D044
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1--
carboxylic acid ethyl ester; [0716] D047
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid methyl ester; [0717] D048
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid ethyl ester; [0718] D051
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid methyl ester; [0719] D052
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid ethyl ester; [0720] D055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0721] D056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0722] D057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid 2-methoxy-ethyl ester; [0723] D060
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0724] D061
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0725] D065
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0726] D066
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0727] D070
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; [0728] D071
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; [0729] D074
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0730] D075
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0731] D078
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0732] D079
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0733] D082
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0734] D083
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0735] D087
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0736] D088
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0737] D092
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0738] D093
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0739] D097
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid methyl ester; [0740] D098
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]-
pyridine-1-carboxylic acid ethyl ester; [0741] D0101
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0742] D0102
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0743] D0105
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0744] D0106
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0745] E01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0746] E02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0747] E05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0748] E06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0749] E09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0750] E010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0751] E013
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0752] E014
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0753] E017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0754] E018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0755] E024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0756] E025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0757] E028
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2--
methoxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0758] E029
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0759] E032
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0760] E033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0761] E036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0762] E037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0763] E040
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethyla-
mino)-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0764] E043
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0765] E044
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0766] E045
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0767] E048
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0768] E052
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0769] E053
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0770] E056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0771] E057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester;
[0772] E060
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0773] E063
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0774] E064
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0775] E065
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0776] E068
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0777] E069
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0778] E072
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethoxy)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0779] E076
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0780] E077
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester and [0781] E080
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester.
[0782] Even most preferred compounds of the present invention are
the following ones: [0783] A02
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0784] A04
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid propyl
ester; [0785] A05
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0786] A08
5-(2,6-Diethyl-phenylcarbamoyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylami-
no]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0787] A024
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0788] A026
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propyl ester; [0789] A027
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0790] A030
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0791] A032
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0792] A042
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0793] A043
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-fluoroethyl ester; [0794] B02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
[0795] B04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmet-
hyl)-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0796] B05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl
ester; [0797] B020
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0798] B021
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid 2-fluoroethyl
ester; [0799] B024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester; [0800] B026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid propyl ester; [0801]
B027
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid isopropyl ester; [0802]
B042
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-pyrrolidin-1-ylmethyl-benzoylam-
ino)-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0803] B046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
ethyl ester; [0804] B048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0805] B049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; [0806] B064
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(2-methyl-2H-pyrazole-3-carbon-
yl)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0807] B068
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid ethyl
ester; [0808] B070
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
propyl ester; [0809] B071
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1-methyl-1H-pyrrole-2-carbony-
l)-amino]-benzoylamino}-furo[3,2-c]pyrazole-1-carboxylic acid
isopropyl ester; [0810] C02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0811] C04
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0812]
C05
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylami-
no)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0813]
C024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0814] C026
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0815] C029
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester; [0816] C046
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0817] C048
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylme-
thyl)-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0818] C049
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0819] C068
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0820]
C070
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl ester; [0821]
C071
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl ester;
[0822] C090
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylm-
ethyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl
ester; [0823] C092
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0824] C093
5-[1-(2-Chloro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-piperidin-1-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0825] C0112
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester;
[0826] C0114
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-yl-
methyl-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0827] C0115
5-[1-(2-Fluoro-phenyl)-1-methyl-ethylcarbamoyl]-3-(4-morpholin-4-ylmethyl-
-benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0828] C0134
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
ethyl ester; [0829] C0136
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
propyl ester; [0830] C0137
3-{2-[(1-Methyl-1H-imidazole-2-carbonyl)-amino]-benzoylamino}-5-(1-methyl-
-1-phenyl-ethylcarbamoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid
isopropyl ester; [0831] C0156
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
[0832] C0158
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-
-ethylcarbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid propyl
ester; [0833] C0159
3-(4-Morpholin-4-yl-benzoylamino)-5-((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl-
carbamoyl)-thieno[3,2-c]pyrazole-1-carboxylic acid isopropyl ester;
[0834] C0178
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)--
amino]-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl
ester; [0835] C0180
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid propyl
ester; [0836] C0181
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-{2-[(1H-pyrrole-3-carbonyl)-amino]-
-benzoylamino}-thieno[2,3-c]pyrazole-1-carboxylic acid isopropyl
ester; [0837] D01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid methyl ester;
[0838] D02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-
-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[-
4,3-c]pyridine-1-carboxylic acid ethyl ester; [0839] D06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0840] D07
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazo-
lo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0841] D11
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0842] D012
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(tetrahydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyraz-
olo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0843] D020
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid methyl ester; [0844] D021
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(tetra-
hydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyr-
idine-1-carboxylic acid ethyl ester; [0845] D024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid methyl ester; [0846] D025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridi-
ne-1-carboxylic acid ethyl ester; [0847] D029
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid ethyl ester; [0848] D033
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid methyl ester; [0849] D034
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-ami-
no]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-
-c]pyridine-1-carboxylic acid ethyl ester; [0850] D038
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid methyl ester; [0851] D039
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl-am-
ino]-2-(2-methoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,-
3-c]pyridine-1-carboxylic acid ethyl ester; [0852] D047
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid methyl ester; [0853] D048
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-met-
hoxy-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine--
1-carboxylic acid ethyl ester; [0854] D051
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid methyl ester; [0855] D052
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-c-
arboxylic acid ethyl ester; [0856] D055
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0857] D056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0858] D060
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0859] D061
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0860] D064
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0861] D066
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0862] D074
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0863] D075
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0864] D078
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0865] D079
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0866] D082
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid methyl ester; [0867] D083
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0868] D087
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0869] D088
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-ethyl)-methyl-a-
mino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-p-
yrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0870] D092
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid methyl ester; [0871] D093
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-[(2-dimethylamino-propyl)-methyl--
amino]-2-(2-methoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro--
pyrazolo[4,3-c]pyridine-1-carboxylic acid ethyl ester; [0872] D0101
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid methyl ester; [0873] D0102
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-pyrrolidin-1-yl-ethoxy)-2-(2-m-
ethoxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3--
c]pyridine-1-carboxylic acid ethyl ester; [0874] D0105
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid methyl ester; [0875] D0106
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]p-
yridine-1-carboxylic acid ethyl ester; [0876] E01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0877] E02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
2-methoxy-ethyl ester; [0878] E05
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0879] E06
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0880] E09
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0881] E010
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0882] E017
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0883] E018
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(tetrahyd-
ro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0884] E024
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0885] E025
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0886] E028
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2--
methoxy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0887] E029
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-metho-
xy-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester; [0888] E036
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid methyl
ester; [0889] E037
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-methox-
y-ethylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl ester;
[0890] E040
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethyla-
mino)-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0891] E043
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0892] E044
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0893] E045
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0894] E048
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0895] E056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0896] E057
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0897] E060
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0898] E063
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0899] E064
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0900] E065
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-ethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0901] E068
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0902] E069
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(2-dimethylamino-propyl)-2-(2-met-
hoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0903] E076
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
methyl ester; [0904] E077
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(pyrrolidin-1-ylmethyl)-2-(2-meth-
oxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester and [0905] E080
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester.
[0906] Lastly, the most preferred compounds are listed below:
[0907] A024
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid ethyl
ester; [0908] A026
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propyl ester; [0909] A027
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester; [0910] A030
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid butyl
ester; [0911] A032
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester; [0912] A042
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoyla-
mino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester; [0913] B02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-[4-(4-methyl-piperazin-1-ylmethyl)-
-benzoylamino]-furo[3,2-c]pyrazole-1-carboxylic acid ethyl ester;
[0914] C02
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoy-
lamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0915]
C024
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-morpholin-4-yl-benzoylamino)-th-
ieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0916] C068
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarb-
amoyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester; [0917]
D02
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyri-
dine-1-carboxylic acid ethyl ester; [0918] D029
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-1-
-carboxylic acid ethyl ester; [0919] D056
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0920] D083
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-1-methyl-ethylamino)-4-
-(4-methyl-piperazin-1-yl)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c-
]pyridine-1-carboxylic acid ethyl ester; [0921] E01
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrah-
ydro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid
ethyl ester; [0922] E040
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0923] E043
S-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester; [0924] E060
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)-
-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester; [0925] E063
R-5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(2-me-
thoxy-1-methyl-ethylamino)-benzoylamino]-indazole-1-carboxylic acid
2-(2-methoxy-ethoxy)-ethyl ester and [0926] E080
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl--
piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester.
[0927] As formerly indicated, the process for preparing the
compounds of formula (I) represents a further object of the
invention.
[0928] The compounds of formula (I) and the pharmaceutically
acceptable salt thereof can be thus prepared according to a process
comprising:
a) reacting an optionally protected bi-cyclic compound of formula
(II):
##STR00026##
wherein A, R.sub.1, R.sub.2 and m are as defined above, with any
suitable agent for inserting the desired --C(O)OR group wherein R
is as defined above on one of the pyrazole nitrogen atoms, such as
a chloroformate derivative, followed by optional removal of the
protecting group, if present; b) if necessary converting the
resultant compound of formula (I):
##STR00027##
wherein A, R, R.sub.1, R.sub.2 and m are as defined above, into
another compound of formula (I) wherein one or more of R.sub.1,
R.sub.2 or m is different by known reactions; separating if
necessary the obtained isomers of formula (Ia) and (Ib) as defined
above according to well-known methods; converting a compound of
formula (I) as defined above into a pharmaceutically acceptable
salt or converting the salt thereof into the free compound of
formula (I) as defined above.
[0929] For a reference to any specific compound of formula (I) of
the invention, optionally in the form of a pharmaceutically
acceptable salt, see the following experimental section.
[0930] Alternatively, the compounds of the formula (I) of present
invention may also be obtained by means of well known method
described in the patent literature cited above, wherein such
compounds are described as useful intermediates.
[0931] It is to be noted that also the compounds of formula (II) as
above defined can be in any one of its tautomeric forms a or b, not
only in the a form depicted above:
##STR00028##
[0932] The above processes are analogy processes, which can be
carried out according to methods known in the art.
[0933] As stated above, it is clear to the person skilled in the
art that if a compound of formula (I), prepared according to the
above process, is obtained as an admixture of isomers, their
separation into the single isomers of formula (I), carried out
according to conventional techniques, is still within the scope of
the present invention.
[0934] According to step (a) of the process, the fused-pyrazole
derivative of formula (II) is reacted, according to well-known
methods, with an agent for introducing the desired carbamoyl group
(--COOR) on one of the pyrazole nitrogen atoms. As an example, the
above reaction may occur with an alkyl chloroformate, also named
chlorocarbonate, in a suitable solvent such as tetrahydrofuran,
dichloromethane, chloroform, acetonitrile, toluene or mixtures
thereof, at a temperature ranging from about -5.degree. C. to about
35.degree. C. and for a time varying from about 30 minutes to about
72 hours, in the presence of an opportune proton scavenger such as
triethylamine or diisopropylethylamine.
[0935] From the above it is clear to the skilled person that this
reaction may be accomplished in a variety of ways and operative
conditions, which are widely known in the art for the preparation
of carbamoyl derivatives.
[0936] For a reference to the preparation of the starting compounds
of formula (II) see the published patent application cited
above.
Pharmacology
[0937] As stated above, the compounds of formula (I) of the present
invention can use as medicament, and in particular as prodrugs for
releasing the active parent drug, according to formula (IA):
##STR00029##
wherein A, R.sub.1, R.sub.2 and m are as defined above defined, in
vivo.
[0938] The released compounds of formula (IA) are active as protein
kinase inhibitors, more particularly Aurora kinases inhibitors or
IGF-R.sub.1 inhibitors and are therefore useful, for instance, to
restrict the unregulated proliferation of tumor cells.
[0939] In therapy, they may be used in the treatment of various
tumors, such as those formerly reported, as well as in the
treatment of other cell proliferative disorders such as psoriasis,
vascular smooth cell proliferation associated with atherosclerosis
and post-surgical stenosis and restenosis.
[0940] The inhibiting activity and the potency of selected
compounds is determined through a method of assay based on the use
of the SPA technology (Amersham Pharmacia Biotech).
[0941] The assay consists of the transfer of radioactivity labelled
phosphate moiety by the kinase to a biotinylated substrate. The
resulting 33P-labelled biotinylated product is allowed to bind to
streptavidin-coated SPA beads (biotin capacity 130 pmol/mg), and
light emitted was measured in a scintillation counter.
Inhibition Assay for IGF-1 R Kinase Activity
[0942] The buffers/components used in the assay were as follows.
Kinase Buffer (buffer KB) was composed of 50 mM HEPES, 3 mM MnCl2,
1 mM DTT, 3 microM Na3VO4, pH 7.9. Enzyme Buffer (buffer EB) was
composed of buffer KB containing 0.6 mg/ml BSA (bovine serum
albumin). SPA scintillation beads (Product Code Number RPNQ0007,
Amersham Biosciences, Piscataway, N.J. USA) were prepared as a 10
mg/ml suspension in PBS containing 32 mM EDTA, 500 microM unlabeled
ATP, and 0.1% Triton X-100. This preparation is referred to below
as "SPA bead suspension". On the day of assay, IGF-1R was
pre-phosphorylated in order to linearize reaction kinetics. To
achieve this, the desired quantity of enzyme was incubated for 30
min at 28.degree. C. at a concentration of 1050 nM enzyme in buffer
EB containing 100 microM unlabeled ATP. After preincubation, and
immediately before assay, this pre-phosphorylated IGF-1R kinase
preparation was diluted to an enzyme concentration of 60 nM by
addition of 16.5 volumes of buffer KB. This diluted
prephosphorylated enzyme is referred to below as "enzyme mix".
[0943] The substrate used in the assay was a carboxy-terminally
biotinylated peptide of the following sequence:
KKKSPGEYVNIEFGGGGGK-biotin. The peptide was obtained in batches of
>95% peptide purity from American Peptide Company, Inc.
(Sunnyvale, Calif., USA). "ATP Mix", referred to below, consisted
of buffer KB containing 6 nM 33Pg-ATP (gamma phosphate-labeled,
Redivue.TM. Code Number AH9968, 1000-3000 Ci/mmole, Amersham
Biosciences Piscataway, N.J. USA), 18 microM unlabeled ATP, and 30
microM biotinylated substrate peptide. This solution contained
these components at 3.times. their final reaction concentrations.
Compounds to be tested were prepared in 100% DMSO at appropriate
concentrations. These preparations were then diluted 33-fold using
buffer KB, so as to obtain compound at 3.times. the desired final
assay concentration in buffer KB containing 3% DMSO. This 3.times.
preparation is referred to below as "compound working
solution".
[0944] Kinase reaction: Reactions were performed in 96-well
U-bottom microtiter plates (such as Product #650101, Greiner
Bio-One, Kremsmuenster Austria) in a final reaction volume of 30
microL. To each test well were added 10 microL of "compound working
solution" containing appropriate dilution of compound, followed by
10 microL "ATP Mix" and 10 microL "Enzyme Mix", thus starting the
reaction. Well contents were immediately mixed by pipetting, and
reactions were incubated for 60 minutes at room temperature. After
incubation, reactions were stopped by adding 100 microL/well "SPA
bead suspension". Wells were incubated a further 15 minutes at room
temperature, then 110 microL were withdrawn from each well and
transferred to separate wells of 96-well opaque scintillation
counting plates (such as OptiPlate.TM.-96, PerkinElmer LAS, Inc.
Boston, Mass., USA), each containing 100 microL/well 5M CsCl. After
4 hours resting at room temperature to allow SPA bead floatation,
these plates were read using a scintillation counter (Packard
TopCount NXT, PerkinElmer LAS, Inc. Boston, Mass., USA) in order to
quantitate the light emitted from each well (proportional to the
amount of phosphate incorporated into the substrate peptide during
kinase reaction).
[0945] Many of the steps described above, such as those involving
compound dilution, addition of mixes to the reaction, and transfer
of completed reaction to counting plates can be automated using
robotized pipetting stations (such as Multimek and Biomek liquid
handlers, Beckman Coulter Inc.,
[0946] Fullerton Calif. USA), and a dilution curve of a known
kinase inhibitor such as staurosporine can be routinely included as
a positive control for IGF-1R inhibition.
[0947] Results: data were analysed using the "Assay Explorer"
software package (Elsevier MDL, San Leandro, Calif. 94577). For
single compound concentrations, inhibitory activity was typically
expressed as expressed as % inhibition obtained in presence of
compound, compared to total activity of enzyme obtained when
inhibitor is omitted. Compounds showing desired inhibition can be
further analysed in order to study the potency of the inhibitor
through IC50 calculation. In this case, inhibition data obtained
using serial dilutions of the inhibitor can be fitted by non-linear
regression using the following equation:
v = v 0 + ( v 0 - v b ) 1 + 10 n ( log IC 50 - log [ I ] )
##EQU00001##
where vb is the baseline velocity, v is the observed reaction
velocity, vo is the velocity in the absence of inhibitors, and [I]
is the inhibitor concentration. Western Blot Analysis of Receptor
Phosphorylation Following Stimulation with IGF-1 in MCF-7 Human
Breast Cancer Cells
[0948] MCF-7 cells (ATCC# HTB-22) were seeded in 12-well tissue
culture plates at 2.times.10''5 cells/well in E-MEM medium (MEM+
Earle's BSS+ 2 mM glutamine+0.1 mM non-essential amino acids)+10%
FCS, and incubated overnight at 37.degree. C., 5% CO2, 100%
relative humidity. Cells were then starved by replacing E-MEM +10%
FCS with E-MEM +0.1% BSA, and incubating overnight. After this
incubation, wells were treated with desired concentrations of
compound for 1 hour at 37.degree. C., and were then stimulated with
10 nM recombinant human IGF-1 (Invitrogen, Carlsbad, Calif., USA)
for 10 minutes at 37.degree. C. Cells were then washed with PBS and
lysed in 100 microL/well cell lysis buffer (M-PER Mammalian Protein
Extraction Reagent [Product #78501, Pierce, Rockford, Ill., USA]+10
mM EDTA+ Protease inhibitor cocktail [Sigma-Aldrich product
#P8340]+ phosphatase inhibitor cocktail [Sigma-Aldrich products
#P2850+#P5726]). Cell lysates were cleared by centrifugation at
10,000.times.g for 5 minutes, and 10 microg/lane of cleared lysate
protein were run on NuPAGE gels (NuPAGE 4-12% 10-lane Bis-Tris
gels, Invitrogen) with MOPS running buffer, then transferred onto
Hybond-ECL nitrocellulose filters (Amersham Biosciences, Little
Chalfont, Buckinghamshire, UK) using Mini PROTEAN II chambers
(Bio-Rad Laboratories, Hercules, Calif., USA). Filters bearing
transferred protein were incubated for 1 hour in blocking buffer
(TBS+5% BSA+0.15% Tween 20), and probed for 2 hours in the same
buffer containing 1/1000 rabbit anti-phospho IGF-1R Tyr1131/InsR
Tyr 1146 antibody (product #3021, Cell Signaling Technology,
Beverly, Mass., USA) for the detection of phosphorylated IGF-1R, or
1/1000 dilution of rabbit IGF-1r.beta.(H-60) antibody (product
#sc-9038, Santa Cruz Biotechnology, Inc., Santa Cruz, Calif., USA)
for detecting total IGF-1R .beta. chain. In either case, filters
were then washed for 30 minutes with several changes of TBS+0.15%
Tween 20, and incubated for 1 hour in washing buffer containing
1/5000 dilution of horseradish peroxidase conjugated anti-rabbit
IgG (Amersham, product #NA934), then were washed again and
developed using the ECL chemiluminescence system (Amersham)
according to manufacturer's recommendations. Unless otherwise
stated, reagents used were from Sigma-Aldrich, St. Louis, Mo.,
USA.
Growth Factor Induced S6 Ribosomal Protein Phosphorylation in
Primary Human Fibroblasts.
[0949] Phosphorylation of S6 ribosomal protein in response to
growth factor stimulation of normal human dermal fibroblasts (NHDF)
was used to assess compound potency in inhibiting IGF-1 induced
signal transduction in cells, and selectivity towards EGF and PDGF
stimulus. NHDF cells obtained from PromoCell (Heidelberg, Germany),
were maintained at 37.degree. C. in a humidified atmosphere with 5%
CO2 in complete Fibroblast Growth Medium (PromoCell). For assay,
NHDF were seeded in 384-well tissue culture plates (clear- and
flat-bottomed black plates; Matrix Technologies Inc., Hudson, N.H.,
USA) at a density of 5000 cells/well in serum-free medium
containing 0.1% bovine serum albumin (BSA) and incubated for 5
days. Starved cells were treated for 1 hour with desired doses of
compounds and then stimulated for a further 2 hours with either 10
nM IGF-1 (Invitrogen Corp., CA, USA), 10 nM EGF (Gibco BRL, USA) or
1 nM PDGF-B/B (Roche Diagnostics GmbH, Germany). Cells were then
fixed in PBS/3.7% paraformaldehyde for 20 minutes at room
temperature, washed .times.2 with PBS, and permeabilized with
PBS/0.3% Triton X-100 for 15 minutes. Wells were then saturated
with PBS/1% non-fat dry milk (Bio-Rad Laboratories, Hercules,
Calif., USA) for 1 hour, and then probed for 1 hour at 37.degree.
C. with anti-phospho-S6 (Ser 235/236) antibody (Cell Signaling
Technology, Beverly, Mass., USA, cat. #2211) at 1/200 dilution in
PBS/1% milk/0.3% Tween 20. Wells were then washed twice with PBS,
and incubated for 1 hour at 37.degree. C. with PBS/1%
milk/0.3.degree. A Tween 20+1 microg/mL DAPI
(4,6-diamidino-2-phenylindole)+1/500 Goat anti-rabbit
Cy5.TM.-conjugated secondary antibody (Amersham Biosciences, Little
Chalfont, Buckinghamshire, UK). Wells were then washed .times.2
with PBS, and 40 microL PBS are left in each well for
immunofluorescence analysis. Fluorescence images in the DAPI and
Cy5.TM. channels were automatically acquired, stored and analysed
using a Cellomics ArrayScan.TM. IV instrument (Cellomics,
Pittsburgh, USA); the Cellomics Cytotoxicity Algorithm was used to
quantify cytoplasmic fluorescence associated with phospho-S6
(Cy5.TM. signal parameter: "Mean Lyso Mass-pH") for each cell in 10
fields/well, and eventually expressed as a mean population value.
Unless otherwise stated, reagents were obtained from Sigma-Aldrich,
St. Louis, Mo., USA.
Inhibition Assay of Aurora-2 Activity
[0950] Kinase reaction: 8 biotinylated peptide (4 repeats of
LRRWSLG), 10 ATP (0.5 uCi P.sup.33-ATP), 7.5 ng Aurora 2, inhibitor
in a final volume of 30 l buffer (HEPES 50 mM pH 7.0, MgCl2 10 mM,
1 mM DTT, 0.2 mg/mL BSA, 3 M orthovanadate) were added to each well
of a 96 U bottom well plate. After 60 minutes at room temperature
incubation, reaction was stopped and biotinylated peptide captured
by adding 100 l of bead suspension.
[0951] Stratification: 100 l of CsCl 5 M were added to each well
and let stand 4 hour before radioactivity was counted in the
Top-Count instrument.
[0952] IC50 determination: inhibitors were tested at different
concentrations ranging from 0.0015 to 10 M. Experimental data were
analyzed by the computer program GraphPad Prizm using the four
parameter logistic equation:
y=bottom+(top-bottom)/(1+10 ((log IC50-x)*slope))
where x is the logarithm of the inhibitor concentration, y is the
response; y starts at bottom and goes to top with a sigmoid
shape.
Ki Calculation:
[0953] Experimental method: Reaction was carried out in buffer (10
mM Tris, pH 7.5, 10 mM MgCl.sub.2, 0.2 mg/mL BSA, 7.5 mM DTT)
containing 3.7 nM enzyme, histone and ATP (constant ratio of
cold/labeled ATP 1/3000). Reaction was stopped with EDTA and the
substrate captured on phosphomembrane (Multiscreen 96 well plates
from Millipore). After extensive washing, the multiscreen plates
were read on a top counter. Control (time zero) for each ATP and
histone concentrations was measured.
[0954] Experimental design: Reaction velocities are measured at
four ATP, substrate (histone) and inhibitor concentrations. An
80-point concentration matrix was designed around the respective
ATP and substrate Km values, and the inhibitor IC50 values (0.3, 1,
3, 9 fold the Km or IC50 values). A preliminary time course
experiment in the absence of inhibitor and at the different ATP and
substrate concentrations allows the selection of a single endpoint
time (10 min) in the linear range of the reaction for the Ki
determination experiment.
[0955] Kinetic parameter estimates: Kinetic parameters were
estimated by simultaneous nonlinear least-square regression using
[Eq.1] (competitive inhibitor respect to ATP, random mechanism)
using the complete data set (80 points):
v = Vm A B .alpha. Ka Kb + .alpha. Ka B + .alpha. Kb A + A B +
.alpha. Ka Ki I ( Kb + B .beta. ) [ Eq . 1 ] ##EQU00002##
[0956] where A=[ATP], B=[Substrate], I=[inhibitor], Vm=maximum
velocity, Ka, Kb, Ki the dissociation constants of ATP, substrate
and inhibitor respectively. and the cooperativity factor between
substrate and ATP binding and substrate and inhibitor binding
respectively.
[0957] The compounds of the invention were further tested, in
vitro, to assess the anti-proliferative effect onto cell
cultures.
In Vitro Cell Proliferation Assay
[0958] The human colon cancer cell line HCT-116 was seeded at 5000
cells/cm.sup.2 in 24 wells plate (Costar) using F12 medium (Gibco)
supplemented with 10% FCS (EuroClone, Italy) 2 mM L-glutamine and
1% penicillin/streptomycin and maintained at 37.degree. C., 5% CO2
and 96% relative humidity. The following day, plates were treated
in duplicates with 5 ul of an appropriate dilution of compounds
starting from a 10 mM stock in DMSO. Two untreated control wells
were included in each plate. After 72 hours of treatment, medium
was withdrawn and cells detached from each well using 0.5 mL of
0.05% (w/v) Trypsin, 0.02% (w/v) EDTA (Gibco). Samples were diluted
with 9.5 mL of Isoton (Coulter) and counted using a Multisizer 3
cell counter (Beckman Coulter). Data were evaluated as percent of
the control wells:
% of CTR=(Treated-Blank)/(Control-Blank).
[0959] IC.sub.50 values were calculated by LSW/Data Analysis using
Microsoft Excel sigmoidal curve fitting. As stated above, the
compounds of formula (I) of the invention resulted to be very
useful as medicament, preferably as prodrugs, even more preferably
as prodrugs for the treatment of diseases due to the malfunctioning
of protein kinases (PKs), such tumors.
BIOAVAILABILITY EXAMPLES
[0960] The following table I reporting the experimental data of
some representative compounds of the invention being tested. The
compounds of formula (I), formulated in 0.5% Methocel.RTM., were
administered orally to mice (10 to 100 mg/Kg) in pharmacokinetic
studies and the conversion of the compounds of formula (I) into the
corresponding parent active compound (IA) as defined above (i.e.
without the --COOR group, wherein R is as defined above) was
monitored in blood by HPLC/MS analysis at 15 and 30 min, 1, 6 and
24 h post-dosing. All blood samples were taken from saphenous
vein.
[0961] Oral bioavailability (Fos) was calculated as percent ratio
of average oral AUC value of parent compound after prodrug to
average IV AUC value of parent compound after parent compound
itself following parent compound dose normalization.
TABLE-US-00001 Identification or Compound Code Fos (mouse)
N-[5-((R)-2-Methoxy-2-phenyl-acetyl)-1,4,5,6-tetrahydro-pyrrolo[3,4-
Parent 1 c]pyrazol-3-yl]-4-(4-methyl-piperazin-1-yl)-benzamide
Compound
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-
A024 13
benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazoles-1-carboxylic
acid ethyl ester
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-
A027 27
benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic
acid isopropyl ester
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-
A042 16
benzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic
acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester
N-[5-(3,5-Difluoro-benzenesulfonyl)- Parent 53
1H-indazol-3-yl]-2-((R)-2-methoxy- Compound
1-methyl-ethylamino)-4-(4-methyl-piperazin- 1-yl)-benzamide
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl- E060
100
ethylamino)-4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-
carboxylic acid ethyl ester
3-(4-Piperidin-1-ylmethyl-benzoylamino)-1H-thieno[2,3-c]pyrazole-
Parent 5 5-carboxylic acid (1-methyl-1-phenyl-ethyl)-amide Compound
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl- C02
33 benzoylamino)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl
ester
[0962] Moreover, the tested compounds resulted to possess also a
very remarkable cell antiproliferative effect. From all of the
above, the compounds of formula (I) of the invention appear to be
endowed with a biological profile, considered as a whole, which is
unexpectedly superior to that of the prior art and, hence, are
particularly advantageous, in therapy, against proliferative
disorders associated with an altered kinase activity, in particular
altered Aurora-2 kinase activity.
[0963] The compounds of the present invention can be administered
either as single agents or, alternatively, in combination with
known anticancer treatments such as radiation therapy or
chemotherapy regimen in combination with cytostatic or cytotoxic
agents, antibiotic-type agents, alkylating agents, antimetabolite
agents, hormonal agents, immunological agents, interferon-type
agents, cyclooxygenase inhibitors (e.g. COX-2 inhibitors),
matrixmetalloprotease inhibitors, telomerase inhibitors, tyrosine
kinase inhibitors, anti-growth factor receptor agents, anti-HER
agents, anti-EGFR agents, anti-angiogenesis agents (e.g.
angiogenesis inhibitors), farnesyl transferase inhibitors, ras-raf
signal transduction pathway inhibitors, cell cycle inhibitors,
other cdks inhibitors, tubulin binding agents, topoisomerase I
inhibitors, topoisomerase II inhibitors, and the like.
[0964] If formulated as a fixed dose, such combination products
employ the compounds of this invention within the dosage range
described below and the other pharmaceutically active agent within
the approved dosage range.
[0965] Compounds of formula (I) may be used sequentially with known
anticancer agents when a combination formulation is
inappropriate.
[0966] The compounds of formula (I) of the present invention,
suitable for administration to a mammal, e.g., to humans, can be
administered by the usual routes and the dosage level depends upon
the age, weight, and conditions of the patient and administration
route.
[0967] For example, a suitable dosage adopted for oral
administration of a compound of formula (I) may range from about 10
to about 500 mg per dose, from 1 to 5 times daily. The compounds of
the invention can be administered in a variety of dosage forms,
e.g., orally, in the form tablets, capsules, sugar or film coated
tablets, liquid solutions or suspensions; rectally in the form
suppositories; parenterally, e.g., intramuscularly, or through
intravenous and/or intrathecal and/or intraspinal injection or
infusion.
[0968] The present invention also includes pharmaceutical
compositions comprising a compound of formula (I) or a
pharmaceutically acceptable salt thereof in association with a
pharmaceutically acceptable excipient, which may be a carrier or a
diluent.
[0969] Another object is therefore the use of a compound of formula
(I) or a pharmaceutically acceptable salt thereof, as defined
above, in the manufacture of a medicament for treating a disease
caused by and/or associated with a dysregulated protein kinase
activity, in particular for treating a disease caused by and/or
associated with a dysregulated IGF-1R or Aurora kinases activity,
preferably with a dysregulated Aurora kinase activity. Such
medicament also provides tumor angiogenesis and metastasis
inhibition.
[0970] The treated disease is preferably selected from the group
consisting of cancer, cell proliferative disorders, viral
infections, retinopathies including diabetic and neonatal
retinopathies and age related macular degeneration, atherosclerosis
and conditions involving vascular smooth muscle proliferation or
neointimal formation such as restenosis following angioplasty or
surgery, graft vessel disease, such as can occur following vessel
or organ transplantation, acromegaly and disorders secondary to
acromegaly as well as other hypertrophic conditions in which
IGF/IGF-1R signalling is implicated, such as benign prostatic
hyperplasia, psoriasis, fibrotic lung disease, pulmonary fibrosis,
pathologies related to chronic or acute oxidative stress or
hyperoxia induced tissue damage, and metabolic disorders in which
elevated IGF levels or IGF-1R activity are implicated, such as
obesity.
[0971] Another object of the present invention is the use of a
compound of formula (I) or a pharmaceutically acceptable salt
thereof, as defined above, in the manufacture of a medicament with
antitumor activity.
[0972] According to the invention, the treated cancer is selected
from the group consisting of carcinoma, squamous cell carcinoma,
hematopoietic tumors of myeloid or lymphoid lineage, tumors of
mesenchymal origin, tumors of the central and peripheral nervous
system, melanoma, seminoma, teratocarcinoma, osteosarcoma,
xeroderma pigmentosum, keratocanthomas, thyroid follicular cancer
and Kaposi's sarcoma.
[0973] Moreover, the treated cancer can be selected from the group
consisting of breast cancer, lung cancer, colorectal cancer,
prostate cancer, ovarian cancer, endometrial cancer, gastric
cancer, clear cell renal cell carcinoma, uveal melanoma, multiple
myeloma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi' sarcoma and
medulloblastoma.
[0974] The treated cell proliferative disorder is selected from the
group consisting of benign prostate hyperplasia, familial
adenomatosis polyposis, neuro-fibromatosis, psoriasis, vascular
smooth cell proliferation associated with atherosclerosis,
pulmonary fibrosis, arthritis, glomerulonephritis and post-surgical
stenosis and restenosis.
[0975] The pharmaceutical compositions containing the compounds of
the invention are usually prepared following conventional methods
and are administered in a suitable pharmaceutical form.
[0976] For example, the solid oral forms may contain, together with
the active compound, diluents, e.g., lactose, dextrose saccharose,
sucrose, cellulose, corn starch or potato starch; lubricants, e.g.,
silica, talc, stearic acid, magnesium or calcium stearate, and/or
polyethylene glycols; binding agents, e.g., starches, arabic gum,
gelatine methylcellulose, carboxymethylcellulose or polyvinyl
pyrrolidone; disintegrating agents, e.g., starch, alginic acid,
alginates or sodium starch glycolate; effervescing mixtures;
dyestuffs; sweeteners; wetting agents such as lecithin,
polysorbates, laurylsulphates; and, in general, non-toxic and
pharmacologically inactive substances used in pharmaceutical
formulations. These pharmaceutical preparations may be manufactured
in known manner, for example, by means of mixing, granulating,
tabletting, sugar-coating, or film-coating processes.
[0977] The liquid dispersions for oral administration may be, e.g.,
syrups, emulsions and suspensions.
[0978] As an example the syrups may contain, as a carrier,
saccharose or saccharose with glycerine and/or mannitol and
sorbitol.
[0979] The suspensions and the emulsions may contain, as examples
of carriers, natural gum, agar, sodium alginate, pectin,
methylcellulose, carboxymethylcellulose, or polyvinyl alcohol.
[0980] The suspension or solutions for intramuscular injections may
contain, together with the active compound, a pharmaceutically
acceptable carrier, e.g., sterile water, olive oil, ethyl oleate,
glycols, e.g., propylene glycol and, if desired, a suitable amount
of lidocaine hydrochloride.
[0981] The solutions for intravenous injections or infusions may
contain, as a carrier, sterile water or preferably they may be in
the form of sterile, aqueous, isotonic, saline solutions or they
may contain propylene glycol as a carrier.
[0982] The suppositories may contain, together with the active
compound, a pharmaceutically acceptable carrier, e.g., cocoa
butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid
ester surfactant or lecithin.
EXAMPLES
[0983] The following examples are intended to illustrate but not in
any way limit the invention. While the invention has been described
with reference to specific methods and embodiments, it will be
appreciated that various modifications may be made without
departing from the invention.
Example 1
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyrid-
ine-1-carboxylic acid ethyl ester (D02)
##STR00030##
[0985] To a solution of
N-[5-(3,5-difluoro-benzenesulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]-
pyridin-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-b-
enzamide (1.38 g, 2.24 mmol) in anhydrous THF (150 mL), cooled to
-40.degree. C., under argon, was added lithium
bis(trimethylsilyl)amide 1.0 M in THF (2.35 mL, 2.35 mmol). The
mixture was stirred for 5 min. then ethyl chloroformate (0.225 mL,
2.35 mmol) was added. The reaction was stirred at -40.degree. C.
for 1 h, then was poured in water and extracted with ethyl acetate.
The organic phase was washed with water, brine and dried with
sodium sulfate. After filtration and evaporation the crude was
triturated with ether to give the title compound as white solid
(1.32 g, 86%).
[0986] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 10.49 (bs,
1H), 8.27 (d, J=7.56 Hz, 1H), 7.75 (d, J=9.15 Hz, 1H), 7.70 (m,
1H), 7.57 (m, 2H), 6.22 (dd, J1=2.07 Hz, J2=9.15 Hz, 1H), 6.12 (d,
J=2.07 Hz, 1H), 4.39 (q, J=7.07 Hz, 2H), 4.08 (bs, 2H), 3.82 (m,
2H), 3.73 (m, 1H), 3.55-3.49 (m, 4H), 3.28 (t, J=5.12 Hz, 4H), 3.02
(t, J=5.61 Hz, 2H), 2.43 (t, J=5.12 Hz, 4H), 2.23 (s, 3H), 1.96 (m,
2H), 1.38 (m, 2H), 1.32 (t, J=7.07 Hz, 3H).
Example 2
5-(3,5-Difluoro-benzenesulfonyl)-3-[4-(4-methyl-piperazin-1-yl)-2-(tetrahy-
dro-pyran-4-ylamino)-benzoylamino]-indazole-1-carboxylic acid ethyl
ester (E01)
##STR00031##
[0988] Operating in an analogous way of that described in Example
1, the title compound was obtained.
[0989] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 10.99 (bs,
1H), 8.59 (d, J=1.71 Hz, 1H), 8.35 (d, J=9.02 Hz, 1H), 8.28 (d,
J=7.68 Hz, 1H), 8.25 (dd, J1=1.71 Hz, J2=9.02 Hz, 1H), 7.88 (d,
J=9.15 Hz, 1H), 7.77 (m, 2H), 7.68 (m, 1H), 6.32 (dd, J1=2.07 Hz,
J2=9.15 Hz, 1H), 6.19 (d, J=2.07 Hz, 1H), 4.53 (q, J=7.07 Hz, 2H),
3.85 (m, 2H), 3.77 (m, 1H), 3.53 (m, 2H), 3.40 (m, 4H), 2.76 (m,
4H), 2.47 (s, 3H), 2.00 (m, 2H), 1.45-1.36 (m, 5H).
Example 3
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((S)-2-methoxy-1-methyl-ethylamino)--
4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester (E040)
##STR00032##
[0991] Operating in an analogous way of that described in Example
1, the title compound was obtained.
[0992] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 10.93 (bs,
1H), 8.60 (d, J=1.83 Hz, 1H), 8.35 (d, J=9.02 Hz, 1H), 8.24 (dd,
J1=1.83 Hz, J2=9.02 Hz, 1H), 8.20 (d, J=7.80 Hz, 1H), 7.83 (d,
J=9.02 Hz, 1H), 7.78 (m, 2H), 7.67 (m, 1H), 6.30 (dd, J1=2.32 Hz,
J2=9.02 Hz, 1H), 6.15 (d, J=2.32 Hz, 1H), 4.53 (q, J=7.07 Hz, 2H),
3.86 (m, 1H), 3.39 (m, 2H), 3.31-3.30 (m, 5H), 2.44 (m, 4H), 2.24
(s, 3H), 1.41 (t, J=7.07 Hz, 3H), 1.19 (d, J=6.46 Hz, 3H).
Example 4
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-((R)-2-methoxy-1-methyl-ethylamino)--
4-(4-methyl-piperazin-1-yl)-benzoylamino]-indazole-1-carboxylic
acid ethyl ester (E060)
##STR00033##
[0994] Operating in an analogous way of that described in Example
1, the title compound was obtained.
[0995] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 10.93 (bs,
1H), 8.60 (d, J=1.83 Hz, 1H), 8.35 (d, J=9.02 Hz, 1H), 8.24 (dd,
J1=1.83 Hz, J2=9.02 Hz, 1H), 8.20 (d, J=7.80 Hz, 1H), 7.83 (d,
J=9.02 Hz, 1H), 7.78 (m, 2H), 7.67 (m, 1H), 6.30 (dd, J1=2.32 Hz,
J2=9.02 Hz, 1H), 6.15 (d, J=2.32 Hz, 1H), 4.53 (q, J=7.07 Hz, 2H),
3.86 (m, 1H), 3.39 (m, 2H), 3.31-3.30 (m, 5H), 2.44 (m, 4H), 2.24
(s, 3H), 1.41 (t, J=7.07 Hz, 3H), 1.19 (d, J=6.46 Hz, 3H).
Example 5
5-(3,5-Difluoro-benzenesulfonyl)-3-[2-(2-methoxy-ethylamino)-4-(4-methyl-p-
iperazin-1-yl)-benzoylamino]-indazole-1-carboxylic acid ethyl ester
(E080)
##STR00034##
[0997] Operating in an analogous way of that described in Example
1, the title compound was obtained.
[0998] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 10.94 (bs,
1H), 8.62 (d, J=1.83 Hz, 1H), 8.35 (d, J=9.02 Hz, 1H), 8.24-8.20
(m, 2H), 7.85 (d, J=9.15 Hz, 1H), 7.78 (m, 2H), 7.68 (m, 1H), 6.30
(dd, J1=2.19 Hz, J2=9.15 Hz, 1H), 6.10 (d, J=2.20 Hz, 1H), 4.52 (q,
J=7.07 Hz, 2H), 3.58 (t, J=5.37 Hz, 2H), 3.37-3.30 (m, 9H), 2.44
(t, J=5.0 Hz, 4H), 2.24 (s, 3H), 1.41 (t, J=7.07 Hz, 3H).
Example 6
3-[4-(Isopropylamino-methyl)-benzoylamino]-5-(1-methyl-1-phenyl-ethylcarba-
moyl)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester
(C068)
##STR00035##
[1000] Operating in an analogous way of that described in Example
1, the title compound was obtained.
[1001] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 1.02 (d, 6H),
1.38 (t, 3H), 1.68 (s, 6H), 2.72 (m, 1H), 3.78 (br. S, 2H), 4.48
(q, 2H), 7.18 (m, 1H), 7.29 (m, 2H), 7.38 (m, 2H), 7.51 (m, 2H),
8.08 (m, 2H), 8.36 (s, 1H), 8.87 (br. s, 1H), 11.66 (br. s,
1H).
[1002] [M+H].sup.+ 548; HRMS (ES.sup.+) cald 548.2326, found
548.2310.
Example 7
5-(1-Methyl-1-phenyl-ethylcarbamoyl)-3-(4-piperidin-1-ylmethyl-benzoylamin-
o)-thieno[2,3-c]pyrazole-1-carboxylic acid ethyl ester (C02)
##STR00036##
[1004] To a solution of
3-(4-Piperidin-1-ylmethyl-benzoylamino)-1H-thieno[2,3-c]pyrazole-5-carbox-
ylic acid (1-methyl-1-phenyl-ethyl)-amide (500 mg, 1 mmol) in
anhydrous THF (20 mL), diisopropylethylamine (1.027 ml, 6 mmol) was
added dropwise at room temperature. The reaction was stirred for 5
minutes, and then ethyl chloroformate (130 mg, 0.115 mL, 1.2 mmol)
wais also added dropwise. After stirring for 1 hour, the solvent
was evaporated, the crude taken up with dichloromethane washed
thoroughly with water, brine and dried with sodium sulfate. After
filtration and evaporation the crude was triturated with ethyl
ether to give the title compound as white solid.
[1005] 1H-NMR (400 MHz), .delta. (ppm, DMSO-d.sub.6): 1.39 (t, 3H),
1.47-191 (m, 12H), 2.27-2.99 (m, 4H), 3.53 (m, 1H), 4.38 (m, 1H),
4.52 (q, 2H), 7.19 (m, 1H), 7.31 (m, 2H), 7.39 (m, 2H), 7.73 (m,
2H), 8.20 (m, 2H), 8.37 (s, 1H), 8.88 (br. s, 1H), 11.80 (br. S,
1H).
[1006] [M+H].sup.+ 574; HRMS (ES.sup.+) cald 574.2483, found
574.2463.
Example 8
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid methyl
ester (A023)
[1007] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1008] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.22 (s, 3H),
2.43 (m, 4H), 3.31 (m, 4H), 3.34 (ds, 3H), 3.94 (ds, 3H), 4.36-4.99
(m, 4H), 5.12 (ds, 1H), 6.96 (d, 2H), 7.32-7.45 (m, 5H), 7.93 (dd,
2H), 11.11 (br. s, 1H)
[1009] [M+H].sup.+ 533; HRMS (ES.sup.+) cald 533.2507, found
533.2515
Example 9
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid vinyl
ester (A025)
[1010] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1011] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.23 (s, 3H),
2.45 (m, 4H), 3.34 (m, 4H), 3.35 (ds, 3H), 4.54-4.99 (m, 4H), 5.14
(m, 3H), 6.97 (d, 2H), 7.27 (ddd, 1H), 7.33-7.45 (m, 5H), 7.95 (dd,
2H), 11.20 (d, 1H)
[1012] [M+H].sup.+ 545; HRMS (ES.sup.+) cald 545.2507, found
545.2508
Example 10
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
n-propyl ester (A026)
[1013] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1014] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 0.97 (t, 3H),
1.88 (m, 2H) 2.22 (s, 3H), 2.43 (m, 4H), 3.30 (m, 4H), 3.35 (ds,
3H), 4.30 (q, 2H), 4.53-4.95 (m, 4H), 5.00, 5.13 (s, 13H), 6.96 (d,
2H), 7.33-7.45 (m, 5H), 7.94 (m, 2H), 11.13 (d, 1H)
[1015] [M+H].sup.+ 561; HRMS (ES.sup.+) cald 561.2820, found
561.2816
Example 11
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid allyl
ester (A028)
[1016] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1017] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.22 (s, 3H),
2.43 (m, 4H), 3.31 (m, 4H), 3.35 (ds, 3H), 4.54-4.96 (m, 6H), 5.09,
5.1 (s, 13H), 5.35 (dd, 1H), 5.45 (dd, 1H), 6.02 (m, 1H), 6.95 (d,
2H), 7.34-7.45 (m, 5H), 7.94 (m, 2H), 11.14 (d, 1H)
[1018] [M+H].sup.+ 559; HRMS (ES.sup.+) cald 559.2664, found
559.2651
Example 12
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
propargyl ester (A029)
[1019] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1020] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.22 (s, 3H),
2.44 (m, 4H), 3.31 (m, 4H), 3.35 (ds, 3H), 3.76 3.82 (m, 2H),
4.45-5.14 (m, 6H), 6.98 (d, 2H), 7.34-7.47 (m, 5H), 7.94 (m, 2H),
11.17 (d, 1H)
[1021] [M+H].sup.+ 557; HRMS (ES.sup.+) cald 557.2507, found
557.2504
Example 13
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isopropyl ester (A027)
[1022] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1023] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 1.35 (d, 6H),
2.22 (s, 3H), 2.43 (m, 4H), 3.31 (m, 4H), 3.35 (ds, 3H), 4.53-4.96
(m, 4H), 5.06-5.15 (m, 2H), 6.97 (d, 2H), 7.32-7.45 (m, 5H), 7.94
(m, 2H), 11.13 (d, 1H)
[1024] [M+H].sup.+ 561; HRMS (ES.sup.+) cald 561.2820, found
561.2823
Example 14
[1025]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
n-butyl ester (A030) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1026] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 0.94 (m, 3H),
1.41 (m, 2H), 1.69 (m, 2H), 2.22 (s, 3H), 2.43 (m, 4H), 3.30 (m,
4H), 3.35 (ds, 3H), 4.34 (m, 2H), 4.53-4.94 (m, 4H), 5.09 5.13 (ds,
1H), 6.97 (d, 2H), 7.32-7.44 (m, 5H), 7.94 (m, 2H), 11.13 (d,
1H)
[1027] [M+H].sup.+ 575; HRMS (ES.sup.+) cald 575.2977, found
575.2953
Example 15
[1028]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
isobutyl ester (A032) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1029] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 0.97 (d, 6H),
2.03 (m, 1H), 2.22 (s, 3H), 2.42 (m, 4H), 3.29 (m, 4H), 3.35 (ds,
3H), 4.13 (m, 2H), 4.54-4.95 (m, 4H), 5.09 5.13 (ds, 1H), 6.98 (d,
2H), 7.32-7.45 (m, 5H), 7.94 (m, 2H), 11.13 (d, 1H).
[1030] [M+H].sup.+ 575; HRMS (ES.sup.+) cald 575.2977, found
575.2967
Example 16
[1031]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
tert-butyl ester (A033) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1032] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 1.56 (s, 9H),
2.22 (s, 3H), 2.42 (m, 4H), 3.31 (m, 4H), 3.34 (s, 3H), 4.13 (m,
2H), 4.56-4.95 (m, 4H), 5.10 5.12 (ds, 1H), 6.96 (d, 2H), 7.32-7.45
(m, 5H), 7.94 (m, 2H), 11.11 (d, 1H).
[1033] [M+H].sup.+ 575; HRMS (ES.sup.+) cald 575.2977, found
575.2972
Example 17
[1034]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
2-methoxyethyl ester (A041) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1035] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.22 (s, 3H),
2.42 (m, 4H), 3.29-3.35 (m, 10H), 3.64 (m, 2H), 4.45-4.97 (m, 6H),
5.08 5.13 (ds, 1H), 6.96 (d, 2H), 7.34-7.44 (m, 5H), 7.94 (m, 2H),
11.11 (d, 1H).
[1036] [M+H].sup.+ 577; HRMS (ES.sup.+) cald 577.2769, found
577.2766
Example 18
[1037]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
neopentyl ester (A035) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1038] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 1.00 (s, 9H),
2.22 (s, 3H), 2.44 (m, 4H), 3.29-3.33 (m, 4H), 3.35, 3.36 (ds, 3H),
4.09 (s, 2H), 4.56-4.96 (m, 4H), 5.07, 5.14 (ds, 1H), 6.98 (d, 2H),
7.34-7.46 (m, 5H), 7.94 (m, 2H), 11.13 (d, 1H).
[1039] [M+H].sup.+ 589; HRMS (ES.sup.+) cald 589.3133, found
589.3135
Example 19
[1040]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
n-hexyl ester (A036) Operating in an analogous way of that
described in Example 7, the title compound was obtained.
[1041] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 0.88 (m, 3H),
1.29-1.41 (m, 6H), 1.90 (m, 2H), 2.22 (s, 3H), 2.42 (m, 4H),
3.27-3.32 (m, 4H), 3.33, 3.34 (ds, 3H), 4.34 (m, 2H), 4.54-4.95 (m,
4H), 5.09 5.13 (ds, 1H), 6.96 (d, 2H), 7.32-7.44 (m, 5H), 7.94 (m,
2H), 11.13 (d, 1H).
[1042] [M+H].sup.+ 603; HRMS (ES.sup.+) cald 603.3290, found
603.3289
Example 20
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-benzoylam-
ino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester (A042)
[1043] Operating in an analogous way of that described in Example
7, the title compound was obtained.
[1044] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 0.76 (m, 3H),
0.92, (m, 6H), 1.46-1.96 (m, 7H), 2.06 (m, 2H), 2.23 (s, 3H), 2.44
(m, 4H), 3.29-3.33 (m, 4H), 3.35, 3.37 (ds, 3H), 4.53-4.98 (m, 5H),
5.13 (s, 1H), 6.97 (d, 2H), 7.33-7.45 (m, 5H), 7.94 (m, 2H), 11.15
(d, 1H).
[1045] [M+H].sup.+ 657; HRMS (ES.sup.+) cald 657.3759, found
657.3781
Example 21
[1046]
5-((R)-2-Methoxy-2-phenyl-acetyl)-3-[4-(4-methyl-piperazin-1-yl)-be-
nzoylamino]-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-1-carboxylic acid
benzyl ester (A038) Operating in an analogous way of that described
in Example 7, the title compound was obtained.
[1047] .sup.1H NMR (400 MHz, DMSO-D6) .delta. ppm 2.24 (s, 3H),
2.46 (m, 4H), 3.30 (m, 4H), 3.34 (s, 3H), 4.49-4.94 (m, 4H), 5.01,
5.13 (ds, 1H), 5.42 (s, 2H), 6.97 (d, 2H), 7.31-7.55 (m, 10H), 7.94
(m, 2H), 11.13 (d, 1H)
[1048] [M+H].sup.+ 608; HRMS (ES.sup.+) cald 609.2820, found
609.2823.
Sequence CWU 1
1
2119PRTArtificial Sequencecarboxy-terminally biotinylated peptide
1Lys Lys Lys Ser Pro Gly Glu Tyr Val Asn Ile Glu Phe Gly Gly Gly1 5
10 15Gly Gly Lys27PRTArtificial Sequencebiotinylated peptide 2Leu
Arg Arg Trp Ser Leu Gly1 5
* * * * *