U.S. patent application number 15/120765 was filed with the patent office on 2016-12-22 for endoparasite control agent.
This patent application is currently assigned to THE UNIVERSITY OF TOKYO. The applicant listed for this patent is Nihon Nohyaku Co., Ltd., The University of Tokyo. Invention is credited to Kiyoshi KITA, Masatsugu ODA, Akiyuki SUWA.
Application Number | 20160367532 15/120765 |
Document ID | / |
Family ID | 54055313 |
Filed Date | 2016-12-22 |
United States Patent
Application |
20160367532 |
Kind Code |
A1 |
KITA; Kiyoshi ; et
al. |
December 22, 2016 |
ENDOPARASITE CONTROL AGENT
Abstract
The present invention is intended to provide a novel
parasiticide, antiprotozoal or other endoparasite control agents
which are effective for controlling animal endoparasites that have
been impossible to control by conventional ones. Provided is an
endoparasite control agent comprising, as an active ingredient, a
carboxamide derivative represented by the general formula (I):
##STR00001## or a salt thereof.
Inventors: |
KITA; Kiyoshi; (Tokyo,
JP) ; SUWA; Akiyuki; (Osaka, JP) ; ODA;
Masatsugu; (Osaka, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The University of Tokyo
Nihon Nohyaku Co., Ltd. |
Tokyo
Tokyo |
|
JP
JP |
|
|
Assignee: |
THE UNIVERSITY OF TOKYO
Tokyo
JP
NIHON NOHYAKU CO., LTD.
Tokyo
JP
|
Family ID: |
54055313 |
Appl. No.: |
15/120765 |
Filed: |
March 4, 2015 |
PCT Filed: |
March 4, 2015 |
PCT NO: |
PCT/JP2015/056326 |
371 Date: |
August 23, 2016 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/166 20130101;
C07D 213/61 20130101; C07C 233/73 20130101; C07D 239/60 20130101;
A61P 33/12 20180101; C07D 241/18 20130101; A61P 33/00 20180101;
C07C 233/66 20130101; C07D 263/58 20130101; A61P 33/10 20180101;
C07D 215/227 20130101; C07D 231/20 20130101; C07D 213/643 20130101;
C07D 239/34 20130101; A61K 31/44 20130101; A61P 33/04 20180101;
C07D 241/44 20130101; C07D 277/68 20130101; A61P 33/02 20180101;
A61P 33/06 20180101 |
International
Class: |
A61K 31/44 20060101
A61K031/44; A61K 31/166 20060101 A61K031/166 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 5, 2014 |
JP |
2014-042876 |
Claims
1-11. (canceled)
12. A method for controlling endoparasites, comprising orally or
parenterally administering, to a mammal or a bird, an effective
amount of an endoparasite control agent comprising, as an active
ingredient, a carboxamide derivative represented by the general
formula (I): ##STR00007## wherein A represents a nitrogen atom or a
C--Y.sup.5 group (wherein Y.sup.5 is a hydrogen atom or a
(C.sub.1-C.sub.6) alkyl group), X.sup.1 and X.sup.2 may be the same
or different, and each represent (a1) a hydrogen atom; (a2) a
halogen atom; p0 (a3) a (C.sub.1-C.sub.6) alkyl group; (a4) a halo
(C.sub.1-C.sub.6) alkyl group; (a5) a (C.sub.1-C.sub.6) alkoxy
group; or (a6) a halo (C.sub.1-C.sub.6) alkoxy group, R.sup.1 and
R.sup.2 may be the same or different, and are selected from the
group consisting of (b1) a hydrogen atom; (b2) a halogen atom; (b3)
a (C.sub.1-C.sub.6) alkyl group; (b4) a (C.sub.1-C.sub.6) alkoxy
group; and (b5) a halo (C.sub.1-C.sub.6) alkyl group, or optionally
(b6) R.sup.1 and R.sup.2 together with the carbon atom bound to
R.sup.1 and R.sup.2 form a (C.sub.3-C.sub.6) cycloalkane, R.sup.3
and R.sup.4 may be the same or different, and are selected from the
group consisting of (c1) a hydrogen atom; (c2) a halogen atom; (c3)
a (C.sub.1-C.sub.6) alkyl group; (c4) a (C.sub.1-C.sub.6) alkoxy
group; and (c5) a halo (C.sub.1-C.sub.6) alkyl group; or optionally
(c6) R.sup.3 and R.sup.4 together with the carbon atom bound to
R.sup.3 and R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane, Y.sup.1
represents (d1) a hydrogen atom; (d2) a halogen atom; (d3) a
(C.sub.1-C.sub.6) alkyl group; (d4) a halo (C.sub.1-C.sub.6) alkyl
group; (d5) a (C.sub.1-C.sub.6) alkoxy group; or (d6) a halo
(C.sub.1-C.sub.6) alkoxy group, Y.sup.2 and Y.sup.4 may be the same
or different, and each represent (e1) a hydrogen atom; (e2) a
halogen atom; (e3) a (C.sub.1-C.sub.6) alkyl group; (e4) a halo
(C.sub.1-C.sub.6) alkyl group; (e5) a (C.sub.1-C.sub.6) alkoxy
group; or (e6) a halo (C.sub.1-C.sub.6) alkoxy group, and Y.sup.3
represents (f1) a phenyl group; (f2) a phenyl group having, on the
ring, 1 to 5 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; (f3) a phenoxy group; (f4) a phenoxy group having, on
the ring, 1 to 5 substituting groups which may be the same or
different and are selected from the group consisting of (a) a
halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f5) a pyridyl
group; (f6) a pyridyl group having, on the ring, 1 to 4
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; (f7) a pyridyloxy group; (f8) a pyridyloxy group
having, on the ring, 1 to 4 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f9) a pyrimidyloxy group; (f10) a
pyrimidyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f11) a pyrazyloxy
group; (f12) a pyrazyloxy group having, on the ring, 1 to 3
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; (f13) a pyrazolyloxy group; (f14) a pyrazolyloxy
group having, on the ring, 1 to 3 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group, (g) a halo
(C.sub.1-C.sub.6) alkoxy group and (h) a formyl group; (f15) a
quinolyloxy group; (f16) a quinolyloxy group having, on the ring, 1
to 6 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; (f17) a quinoxalyloxy group; (f18) a quinoxalyloxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f19) a benzoxazolyloxy group;
(f20) a benzoxazolyloxy group having, on the ring, 1 to 4
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; (f21) a benzothiazolyloxy group; or (f22) a
benzothiazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group}, or a salt
thereof.
13. The method according to claim 12, wherein the endoparasite
control agent is orally or parenterally administered to a non-human
mammal.
14. The method according to claim 13, wherein the non-human mammal
is a domestic animal.
15. The method according to claim 12, wherein the mammal is a
human.
16. The method according to claim 12, wherein the mammal is a
non-human mammal.
17. The method according to claim 12, wherein A represents a
nitrogen atom or a C--H group, X.sup.1 and X.sup.2 may be the same
or different, and each represent (a1) a hydrogen atom; (a2) a
halogen atom; or (a4) a halo (C.sub.1-C.sub.6) alkyl group, R.sup.1
and R.sup.2 each represent (b1) a hydrogen atom, R.sup.3 and
R.sup.4 may be the same or different, and are selected from the
group consisting of (c1) a hydrogen atom; (c3) a (C.sub.1-C.sub.6)
alkyl group; and (c4) a (C.sub.1-C.sub.6) alkoxy group, or
optionally (c6) R.sup.3 and R.sup.4 together with the carbon atom
bound to R.sup.3 and R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
Y.sup.1 represents (d2) a halogen atom, Y.sup.2 and Y.sup.4 each
represent (e1) a hydrogen atom, and Y.sup.3 is selected from the
group consisting of (f1) a phenyl group; (f2) a phenyl group
having, on the ring, 1 to 5 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f3) a phenoxy group; (f4) a
phenoxy group having, on the ring, 1 to 5 substituting groups which
may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6)
alkoxy group and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f5) a
pyridyl group; (f7) a pyridyloxy group; (f8) a pyridyloxy group
having, on the ring, 1 to 4 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f10) a pyrimidyloxy group having,
on the ring, 1 to 3 substituting groups which may be the same or
different and are selected from the group consisting of (a) a
halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f11) a pyrazyioxy group; (f12) a
pyrazyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f14) a pyrazolyloxy
group having, on the ring, 1 to 3 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group, (g) a halo
(C.sub.1-C.sub.6) alkoxy group and (h) a formyl group; (f15) a
quinolyloxy group; (f17) a quinoxalyloxy group; (f19) a
benzoxazolyloxy group; (f21) a benzothiazolyloxy group; and (f22) a
benzothiazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group.
18. The method according to claim 12, wherein A represents a C--H
group, X.sup.1 and X.sup.2 may be the same or different, and are
selected from the group consisting of (a1) a hydrogen atom; (a2) a
halogen atom; and (a4) a halo (C.sub.1-C.sub.6) alkyl group,
R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom, R.sup.3
and R.sup.4 may be the same or different, and are selected from the
group consisting of (c1) a hydrogen atom; (c3) a (C.sub.1-C.sub.6)
alkyl group; and (c4) a (C.sub.1-C.sub.6) alkoxy group, or
optionally (c6) R.sup.3 and R.sup.4 together with the carbon atom
bound to R.sup.3 and R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
Y.sup.1 represents (d2) a halogen atom, Y.sup.2 and Y.sup.4 each
represent (e1) a hydrogen atom, and Y.sup.3 is selected from the
group consisting of (f1) a phenyl group; (f2) a phenyl group
having, on the ring, 1 to 5 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f3) a phenoxy group; (f4) a
phenoxy group having, on the ring, 1 to 5 substituting groups which
may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6)
alkoxy group and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f5) a
pyridyl group; (f7) a pyridyloxy group; (f8) a pyridyloxy group
having, on the ring, 1 to 4 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f10) a pyrimidyloxy group having,
on the ring, 1 to 3 substituting groups which may be the same or
different and are selected from the group consisting of (a) a
halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f11) a pyrazyloxy group; (f12) a
pyrazyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; (f14) a pyrazolyloxy
group having, on the ring, 1 to 3 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group, (g) a halo
(C.sub.1-C.sub.6) alkoxy group and (h) a formyl group; (f15) a
quinolyloxy group; (f17) a quinoxalyloxy group; (f19) a
benzoxazolyloxy group; (f21) a benzothiazolyloxy group; and (f22) a
benzothiazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group.
19. The method according to claim 12, wherein A represents a
nitrogen atom, X.sup.1 and X.sup.2 may be the same or different,
and are selected from the group consisting of (a1) a hydrogen atom;
(a2) a halogen atom; and (a4) a halo (C.sub.1-C.sub.6) alkyl group,
R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom, R.sup.3
and R.sup.4 may be the same or different, and are selected from the
group consisting of (c1) a hydrogen atom; and (c3) a
(C.sub.1-C.sub.6) alkyl group, Y.sup.1 represents (d2) a halogen
atom; or (d3) a (C.sub.1-C.sub.6) alkyl group, Y.sup.2 and Y.sup.4
each represent (e1) a hydrogen atom, and Y.sup.3 is selected from
the group consisting of (f1) a phenyl group; (f2) a phenyl group
having, on the ring, 1 to 5 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; (f3) a phenoxy group; (f4) a
phenoxy group having, on the ring, 1 to 5 substituting groups which
may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6)
alkoxy group and (g) a halo (C.sub.1-C.sub.6) alkoxy group; and
(f5) a pyridyl group.
Description
FIELD
[0001] The present invention relates an endoparasite control agent
comprising a carboxamide derivative or a salt thereof as an active
ingredient,, and a method for controlling endoparasites, comprising
orally or parenterally administering the endoparasite control
agent.
BACKGROUND ART
[0002] Certain kinds of carboxamide derivatives have been known to
have microbicidal activity (see Patent Literature 1 to 12).
However, the literature does not describe that these compounds are
effective for the disinfection or control of endoparasites in
animals such as mammals and birds. It is also known that certain
kinds of carboxamide derivatives are effective against nematodes
that may damage agricultural products (see Patent Literature 4 or
5), but there is no specific disclosure as to whether these
compounds are effective against endoparasites in animals.
Furthermore, there is a report that compounds that inhibit
succinate-ubiquinone reductase (mitochondrial complex II), which is
one of the respiratory enzymes of endoparasites, can serve as an
endoparasite control agent (see Non Patent Literature 1).
[0003] In addition, Patent Literature 13 discloses certain kinds of
carboxamide derivatives which are effective against endoparasites.
However, there is no disclosure of the effects of the compounds of
the present invention against endoparasites.
[0004] Generally, parasitosis is caused by infestation of host
animals with parasites such as unicellular protists (protozoa),
multicellular helminths and arthropods. It is reported that the
incidence of parasitosis in Japan has been remarkably decreased by
improvement of environmental hygiene, but on a global scale,
particularly in developing countries, parasitosis still widely
prevails and causes tremendous damage. In recent years, there have
been seen the introduction of infection sources via long- or
short-term travelers having visited such countries; parasitic
infection due to the consumption of food imports or raw meat and
fish meat, which have become more available thanks to the advance
in freezing and logistics technologies; and the transmission of
parasitosis from pets. Under such circumstances, the incidence of
parasitosis is on an upward trend again. Another problem is that
immunodeficiency caused by mass administration of
immunosuppressants, anticancer drugs, etc. or by AIDS etc. allows
usually non-pathogenic or low-pathogenic parasites to express their
pathogenicity and to cause opportunistic infection in hosts.
Further, parasitosis in domestic animals, such as pigs, horses,
cattle, sheep, dogs, cats and domestic fowls, is a universal and
serious economic problem. That is, parasitic infection of domestic
animals causes anemia, malnutrition, debility, weight loss, and
serious damage of intestinal tract walls, tissues and organs, and
may result in decline in feed efficiency and productivity, leading
to a great economic loss. Therefore, novel parasiticides,
antiprotozoals or other endoparasite control agents have always
been desired.
CITATION LIST
Patent Literature
[0005] Patent Literature 1: JP-A 01-151546
[0006] Patent Literature 2: WO 2007/060162
[0007] Patent Literature 3: JP-A 53-9739
[0008] Patent Literature 4: WO 2007/108483
[0009] Patent Literature 5: WO 2007/104496
[0010] Patent Literature 6: WO 2008/101975
[0011] Patent Literature 7: WO 2008/101976
[0012] Patent Literature 8: WO 2008/003745
[0013] Patent Literature 9: WO 2008/003746
[0014] Patent Literature 10: WO 2009/012998
[0015] Patent Literature 11: WO 2009/127718
[0016] Patent Literature 12: WO 2010/106971
[0017] Patent Literature 13: WO 2012/118139
Non Patent Literature
[0018] Non Patent Literature 1: Kiyoshi Kita, "Kansen (Infection)",
Winter 2010, Vol. 40-4, 310-319
SUMMARY OF INVENTION
Technical Problem
[0019] In view of the above-described circumstances, the present
invention is mainly intended to provide a novel parasiticide,
antiprotozoal or other endoparasite control agents which are
effective for controlling animal endoparasites that have been
impossible to control by conventional ones.
Solution to Problem
[0020] The present inventors conducted extensive research to solve
the above-described problems. As a result, the present inventors
found that a carboxamide derivative represented by the general
formula (I) of the present invention and a salt thereof are highly
effective for controlling endoparasites. The present inventors
further conducted a great deal of examination and then completed
the present invention. That is, the present invention relates to
the following.
[0021] [1] An endoparasite control agent comprising, as an active
ingredient, a carboxamide derivative represented by the general
formula (I):
##STR00002##
wherein
[0022] A represents a nitrogen atom or a C--Y.sup.5 group (wherein
Y.sup.5 is a hydrogen atom or a (C.sub.1-C.sub.6) alkyl group),
[0023] X.sup.1 and X.sup.2 may be the same or different, and each
represent [0024] (a1) a hydrogen atom; [0025] (a2) a halogen atom;
[0026] (a3) a (C.sub.1-C.sub.6) alkyl group; [0027] (a4) a halo
(C.sub.1-C.sub.6) alkyl group; [0028] (a5) a (C.sub.1-C.sub.6
alkoxy group; or [0029] (a6) a halo (C.sub.1-C.sub.6) alkoxy
group,
[0030] R.sup.1 and R.sup.2 may be the same or different, and are
selected from the group consisting of [0031] (b1) a hydrogen atom;
[0032] (b2) a halogen atorn; [0033] (b3) a (C.sub.1-C.sub.6) alkyi
group; [0034] (b4) a (C.sub.1-C.sub.6) alkoxy group; and [0035]
(b5) a halo (C.sub.1-C.sub.6) alkyl group, or optionally [0036]
(b6) R.sup.1 and R.sup.2 together with the carbon atom bound to
R.sup.1 and R.sup.2 form a (C.sub.3-C.sub.6) cycloalkane,
[0037] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0038] (c1) a hydrogen atom;
[0039] (c2) a halogen atom; [0040] (c3) a (C.sub.1-C.sub.6) alkyl
group; [0041] (c4) a (C.sub.1-C.sub.6) alkoxy group; and [0042]
(c5) a halo (C.sub.1-C.sub.6) alkyl group; or optionally [0043]
(c6) R.sup.3 and R.sup.4 together with the carbon atom bound to
R.sup.3 and R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
[0044] Y.sup.1 represents [0045] (d1) a hydrogen atom; [0046] (d2)
a halogen atom; [0047] (d3) a (C.sub.1-C.sub.6) alkyl group; [0048]
(d4) a halo C.sub.1-C.sub.6) alky group; [0049] (d5) a
(C.sub.1-C.sub.6) alkoxy group; or [0050] (d6) a halo
(C.sub.1-C.sub.6) alkoxy group,
[0051] Y.sup.2 and Y.sup.4 may be the same or different, and each
represent [0052] (e1) a hydrogen atom; [0053] (e2) a halogen atom;
[0054] (e3) a (C.sub.1-C.sub.6) alkyl group; [0055] (e4) a halo
(C.sub.1-C.sub.6) alkyl group; [0056] (e5) a (C.sub.1-C.sub.6)
alkoxy group; or [0057] (e6) a halo (C.sub.1-C.sub.6) alkoxy group,
and
[0058] Y.sup.3 represents [0059] (f1) a phenyl group; [0060] (f2) a
phenyl group having, on the ring, 1 to 5 substituting groups which
may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0061] (f3) a
phenoxy group; [0062] (f4) a phenoxy group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; [0063] (f5) a pyridyl group; [0064]
(f6) a pyridyl group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0065] (f7) a
pyridyloxy group; [0066] (f8) a pyridyloxy group having, on the
ring, 1 to 4 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0067] (f9) a pyrimidyloxy group; [0068] (f10) a
pyrimidyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0069] (f11) a
pyrazyloxy group; [0070] (f12) a pyrazyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0071] (f13) a pyrazolyloxy group; [0072] (f14) a
pyrazolyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy
group, (g) a halo (C.sub.1-C.sub.6) alkoxy group and (h) a formyl
group; [0073] (f15) a quinolyloxy group; [0074] (f16) a quinolyloxy
group having, on the ring, 1 to 6 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group; [0075] (f17) a quinoxalyloxy group;
[0076] (f18) a quinoxalyloxy group having, on the ring, 1 to 5
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0077] (f19) a benzoxazolyloxy group; [0078] (f20) a
benzoxazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxyl group; [0079] (f21) a
benzothiazolyloxy group; or [0080] (f22) a benzothiazolyloxy group
having, on the ring, 1 to 4 substituting groups which may be the
same or different and are selected from the group consisting of (a)
a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (e) a halo (C.sub.1-C.sub.6) alkyl
group, (f) a (C.sub.1-C.sub.6) alkoxy group and (g) a halo
(C.sub.1-C.sub.6) alkoxy group, or a salt thereof.
[0081] [2] The endoparasite control agent according to the above
[1], wherein
[0082] A represents a nitrogen atom or a C--H group,
[0083] X.sup.1 and X.sup.2 may be the same or different, and each
represent [0084] (a1) a hydrogen atom; [0085] (a2) a halogen atom;
or [0086] (a4) a halo (C.sub.1-C.sub.6) alkyl group,
[0087] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0088] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0089] (c1) a hydrogen atom;
[0090] (c3) a (C.sub.1-C.sub.6) alkyl group; and [0091] (c4) a
(C.sub.1-C.sub.6) alkoxy group, or optionally [0092] (c6) R.sup.3
and R.sup.4 together with the carbon atom bound to R.sup.3 and
R.sup.4 form a (C.sub.1-C.sub.6) cycloalkane,
[0093] Y.sup.1 represents (d2) a halogen atom,
[0094] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom,
and
[0095] Y.sup.3 is selected from the group consisting of [0096] (f1)
a phenyl group; [0097] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl groups, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0098] (f3) a phenoxy group; [0099] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0100] (f5) a
pyridyl group; [0101] (f7) a pyridyloxy group;
[0102] (f8) a pyridyloxy group having, on the ring, 1 to 4
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0103] (f10) a pyrimidyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0104] (f11) a pyrazyloxy group; [0105] (f12) a
pyrazyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0106] (f14) a
pyrazolyloxy group having, on the ring, 1 to 3substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy
group, (g) a halo (C.sub.1-C.sub.6) alkoxy group and (h) a formyl
group; [0107] (f15) a quinolyloxy group; [0108] (f17) a
quinoxalyloxy group; [0109] (f19) a benzoxazolyloxy group; [0110]
(f21) a benzothiazolyloxy group; and [0111] (f22) a
benzothiazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group.
[0112] [3] The endoparasite control agent according to the above
[1], wherein
[0113] A represents a C--H group,
[0114] X.sup.1 and X.sup.2 may be the same or different, and are
selected from the group consisting of [0115] (a1) a hydrogen atom;
[0116] (a2) a halogen atom; and [0117] (a4) a halo
(C.sub.1-C.sub.6) alkyl group,
[0118] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0119] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0120] (c1) a hydrogen atom;
[0121] (c3) a (C.sub.1-C.sub.6) alkyl group; and [0122] (c4) a
(C.sub.1-C.sub.6) alkoxy group, or optionally [0123] (c6) R.sup.3
and R.sup.4 together with the carbon atom bound to R.sup.3 and
R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
[0124] Y.sup.1 represents (d2) a halogen atom,
[0125] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom, and
[0126] Y.sup.3 is selected from the group consisting of [0127] (f1)
a phenyl group; [0128] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0129] (f3) a phenoxy group; [0130] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0131] (f5) a
pyridyl group; [0132] (f7) a pyridyloxy group; [0133] (f8) a
pyridyloxy group having, on the ring, 1 to 4 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0134] (f10) a
pyrimidyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0135] (f11) a
pyrazyloxy group; [0136] (f12) a pyrazyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.11-C.sub.6)
alkoxy group; [0137] (f14) a pyrazolyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6C) alkoxy group, (g) a halo (C.sub.1-C.sub.6)
alkoxy group and (h) a formyl group; [0138] (f15) a quinolyloxy
group; [0139] (f17) a quinoxalyloxy group; [0140] (f19) a
benzoxazolyloxy group; [0141] (f21) a benzothiazolyloxy group; and
[0142] (f22) a benzothiazolyloxy group having, on the ring, 1 to 4
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group.
[0143] [4] The endoparasite control agent according to the above
[1], wherein
[0144] A represents a nitrogen atom,
[0145] X.sup.1 and X.sup.2 may be the same or different, and are
selected from the group consisting of [0146] (a1) a hydrogen atom;
[0147] (a2) a halogen atom; and [0148] (a4) a halo
(C.sub.1-C.sub.6) alkyl group,
[0149] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0150] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0151] (c1) a hydrogen atom;
and [0152] (c3) a (C.sub.1-C.sub.6) alkyl group,
[0153] Y.sup.1 represents [0154] (d2) a halogen atom; or [0155]
(d3) a (C.sub.1-C.sub.6) alkyl group,
[0156] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom,
and
[0157] Y.sup.3 is selected from the group consisting of [0158] (f1)
a phenyl group; [0159] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (f) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0160] (f3) a phenoxy group; [0161] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; and [0162] (f5) a
pyridyl group.
[0163] [5] A method for controlling endoparasites, comprising
orally or parenterally administering an effective amount of the
endoparasite control agent according to any one of the above [1] to
[4] to a non-human mammal or a bird.
[0164] [6] A method for controlling endoparasites, comprising
orally or parenterally administering an effective amount of the
endoparasite control agent according to any one of the above [1] to
[4] to a non-human mammal.
[0165] [7] The method according to the above [5]; or [6], wherein
the non-human mammal is a domestic animal.
[0166] [8] A method for controlling endoparasites, comprising
orally or parenterally administering an effective amount of the
endoparasite control agent according to any one of the above [1] to
[4] to a human.
[0167] [9] The carboxamide derivative specified in any one of the
above [1] to [4] or a salt thereof for use in control of
endoparasites.
[0168] [10] Use of the carboxamide derivative specified in any one
of the above [1] to [4] or a salt thereof for production of
endoparasite control agents.
[0169] [11] Use of the carboxamide derivative specified in any one
of the above [1] to [4] or a salt thereof for control of
endoparasites.
Advantageous Effects of Invention
[0170] The present invention provides an endoparasite control agent
having better performance in the disinfection or control of
endoparasites as compared with the conventional art.
DESCRIPTION OF EMBODIMENTS
[0171] The definitions in connection with the general formula (I)
representing the carboxamide derivative of the present invention
are described below.
[0172] The "halogen atom" refers to a chlorine atom, a bromine
atom, an iodine atom or a fluorine atom.
[0173] The "(C.sub.1-C.sub.6) alkyl group" refers to a
straight-chain or branched-chain alkyl group of 1 to 6 carbon
atoms, for example, a methyl group, an ethyl group, a n-propyl
group, an isopropyl group, a n-butyl group, an isobutyl group, a
sec-butyl group, a tert-butyl group, a n-pentyl group, a neopentyl
group, a n-hexyl group or the like.
[0174] The "(C.sub.1-C.sub.6) alkoxy group" refers to a
straight-chain or branched-chain alkoxy group of 1 to 6 carbon
atoms, for example, a methoxy group, an ethoxy group, a n-propoxy
group, an isopropoxy group, a n-butoxy group, a sec-butoxy group, a
tert-butoxy group, a n-pentyloxy group, an isopentyloxy group, a
neopentyloxy group, a n-hexyloxy group or the like.
[0175] The "halo (C.sub.1-C.sub.6) alkyl group" refers to a
straight-chain or branched-chain alkyl group of 1 to 6 carbon atoms
substituted with one or more halogen atoms which may be the same or
different from each other, for example, a trifluoromethyl group, a
difluoromethyl group, a perfluoroethyl group, a hexafluoroisopropyl
group, a perfluoroisopropyl group, a chloromethyl group, a
bromomethyl group, a 1-bromoethyl group, a 2,3-dibromopropyl group
or the like.
[0176] The "halo (C.sub.1-C.sub.6) alkoxy group" refers to a
straight-chain or branched-chain alkoxy group of 1 to 6 carbon
atoms substituted with one or more halogen atoms which may be the
same or different from each other, for example, a trifluoromethoxy
group, a difluoromethoxy group, a perfluoroethoxy group, a
perfluoroisopropoxy group, a chloromethoxy group, a bromomethoxy
group, a 1-bromoethoxy group, a 2,3-dibromopropoxy group or the
like.
[0177] The "(C.sub.3-C.sub.6) cycloalkane" formed of R.sup.1 and
R.sup.2 together with the carbon atom bound to R.sup.1 and R.sup.2
is, for example, cyclopropane, cyclobutane, cyclopentane,
cyclohexane or the like.
[0178] The "(C.sub.3-C.sub.6) cycloalkane" formed of R.sup.3 and
R.sup.4 together with the carbon atom bound to R.sup.3 and R.sup.4
is, for example, cyclopropane, cyclobutane, cyclopentane,
cyclohexane or the like.
[0179] Examples of the salt of the carboxamide derivative
represented by the general formula (I) of the present invention
include inorganic acid salts, such as hydrochlorides, sulfates,
nitrates and phosphates; organic acid salts, such as acetates,
fumarates, maleates, oxalates, methanesulfonates, benzenesulfonates
and p-toluenesulfonates; and salts with an inorganic or organic
base such as a sodium ion, a potassium ion, a calcium ion and a
trimethylammonium ion.
[0180] As the carboxamide derivative of the present invention,
preferred is a compound of the general formula (I) in which
[0181] A represents a nitrogen atom or a C--H group,
[0182] X.sup.1 and X.sup.2 may be the same or different, and each
represent [0183] (a1) a hydrogen atom; [0184] (a2) a halogen atom;
or [0185] (a4) a halo (C.sub.1-C.sub.6) alkyl group,
[0186] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0187] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0188] (c1) a hydrogen atom;
[0189] (c3) a (C.sub.1-C.sub.6) alkyl group; and [0190] (c4) a
(C.sub.1-C.sub.6) alkoxy group, or optionally [0191] (c6) R.sup.3
and R.sup.4 together with the carbon atom bound to R.sup.3 and
R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
[0192] Y.sup.1 represents (d2) a halogen atom,
[0193] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom,
and
[0194] Y.sup.3 is selected from the group consisting of [0195] (f1)
a phenyl group; [0196] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0197] (f3) a phenoxy group; [0198] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0199] (f5) a
pryidyl group; [0200] (f7) a pyridyloxy group; [0201] (f8) a
pyridyloxy group having, on the ring, 1 to 4 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0202] (f10) a
pyrimidyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6)alkoxy group; [0203] (f11) a
pyrazyloxy group; [0204] (f12) a pyrazyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0205] (f14) a pyrazolyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group, (g) a halo (C.sub.1-C.sub.6) alkoxy
group and (h) a formyl group; [0206] (f15) a quinolyloxy group;
[0207] (f17) a quinoxalyloxy group; [0208] (f19) a benzoxazolyoxy
group; [0209] (f21) a benzothiazolyloxy group; and [0210] (f22) a
benzothiazolyloxy group having, on the ring, 1 to 4 substituting
groups which may be the same or different and are selected from the
group consisting of (a) a halogen atom, (b) a cyano group, (c) a
nitro group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group, or a salt
thereof.
[0211] As the carboxamide derivative of the present invention,
further preferred is a compound of the general formula (I) in
which
[0212] A represents a C--H group,
[0213] X.sup.1 and X.sup.2 may be the same or different, and are
selected from the group consisting of [0214] (a1) a hydrogen atom;
[0215] (a2) a halogen atom; and [0216] (a4) a halo
(C.sub.1-C.sub.6) alkyl group,
[0217] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0218] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0219] (c1) a hydrogen atom;
[0220] (c3) a (C.sub.1-C.sub.6) alkyl group; and [0221] (c4) a
(C.sub.1-C.sub.6) alkoxy group, or optionally [0222] (c6) R.sup.3
and R.sup.4 together with the carbon atom bound to R.sup.3 and
R.sup.4 form a (C.sub.3-C.sub.6) cycloalkane,
[0223] Y.sup.1 represents (d2) a halogen atom,
[0224] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom,
and
[0225] Y.sup.3 is selected from the group consisting of [0226] (f1)
a phenyl group; [0227] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0228] (f3) a phenoxy group; [0229] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; [0230] (f5) a
pyridyl group; [0231] (f7) a pyridyloxy group; [0232] (f8) a
pyridyloxy group having, on the ring, 1 to 4 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo ((C.sub.1-C.sub.6) alkoxy group; [0233] (f10) a
pyrimidyloxy group having, on the ring, 1 to 3 substituting groups
which may be the same or different and are selected from the group
consisting of (a) a halogen atom, (b) a cyano group, (c) a nitro
group, (d) a (C.sub.1-C.sub.6) alkyl group, (e) a halo
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6 alkoxy group; [0234] (f11) a
pyrazyloxy group; [0235] (f12) a pyrazyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0236] (e14) a pyrazolyloxy group having, on the
ring, 1 to 3 substituting groups which may be the same or different
and are selected from the group consisting of (a) a halogen atom,
(b) a cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group, (g) a halo (C.sub.1-C.sub.6) alkoxy
group and (h) a formyl group; [0237] (f15) a quinolyloxy group;
[0238] (f17) a quinoxalyloxy group; [0239] (f19) a benzoxazolyloxy
group; [0240] (f21) a benzothiazolyloxy group; and
[0241] (f22) a benzothiazolyloxy group having, on the ring, 1 to 4
substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group, or a salt thereof.
[0242] Also preferred is a compound of the general formula (I) in
which
[0243] A represents a nitrogen atom,
[0244] X.sup.1 and X.sup.2 may be the same or different, and are
selected from the group consisting of [0245] (a1) a hydrogen atom;
[0246] (a2) a halogen atom; and [0247] (a4) a halo
(C.sub.1-C.sub.6) alkyl group,
[0248] R.sup.1 and R.sup.2 each represent (b1) a hydrogen atom,
[0249] R.sup.3 and R.sup.4 may be the same or different, and are
selected from the group consisting of [0250] (c1) a hydrogen atom;
and [0251] (c3) a (C.sub.1-C.sub.6) alkyl group,
[0252] Y.sup.1 represents [0253] (d2) a halogen atom; or [0254]
(d3) a (C.sub.1-C.sub.6) alkyl group,
[0255] Y.sup.2 and Y.sup.4 each represent (e1) a hydrogen atom,
and
[0256] Y.sup.3 is selected from the group consisting of [0257] (f1)
a phenyl group; [0258] (f2) a phenyl group having, on the ring, 1
to 5 substituting groups which may be the same or different and are
selected from the group consisting of (a) a halogen atom, (b) a
cyano group, (c) a nitro group, (d) a (C.sub.1-C.sub.6) alkyl
group, (e) a halo (C.sub.1-C.sub.6) alkyl group, (f) a
(C.sub.1-C.sub.6) alkoxy group and (g) a halo (C.sub.1-C.sub.6)
alkoxy group; [0259] (f3) a phenoxy group; [0260] (f4) a phenoxy
group having, on the ring, 1 to 5 substituting groups which may be
the same or different and are selected from the group consisting of
(a) a halogen atom, (b) a cyano group, (c) a nitro group, (d) a
(C.sub.1-C.sub.6) alkyl group, (f) a (C.sub.1-C.sub.6) alkoxy group
and (g) a halo (C.sub.1-C.sub.6) alkoxy group; and [0261] (f5) a
pyridyl group, or a salt thereof.
[0262] The compound represented by the general formula (I) of the
present invention can be produced by any of the production methods
described in JP-A 01-151546, WO 2007/060162, JP-A 53-9739, WO
2007/108483, WO 2008/101975, WO 2008/101976, WO 2008/003745, WO
2008/003746, WO 2009/012998, WO 2009/127718, WO 2010/106971 and WO
2012/113139, the method described in Shin-Jikken Kagaku Kouza 14
(Maruzen, Dec. 20, 1977), a modified method of the foregoing, or
the like.
[0263] Representative examples of the carboxamide derivative
represented by the general formula (I) of the present invention are
shown in tables 1 and 2, but the present invention is not limited
thereto. In Tables 1 and 2, "MeO" stands for a methoxy group, "Ph"
stands for a phenyl group, "Py" stands for a pyridyl group, "PhO"
stands for a phenoxy group, and "PyO" stands for a pyridyloxy
group. Shown in the column of "Physical property" are mass spectral
data.
[0264] Q1 to Q19 represent the following structures. The black
circle in each of the formulae Q1 to Q19 represents a binding
site.
##STR00003## ##STR00004##
##STR00005##
TABLE-US-00001 TABLE 1 Compound Physical No. X.sup.1 X.sup.2
R.sup.3 R.sup.4 Y.sup.1 Y.sup.3 property 1-1 CF.sub.3 H H H Cl Q3
489 (M + 1) 1-2 CF.sub.3 H H H Cl Q4 535 (M + 1) 1-3 CF.sub.3 H H H
Cl Q5 490 (M + 1) 1-4 CF.sub.3 H H H Cl Q6 456 (M + 1) 1-5 CF.sub.3
H H H Cl Q7 422 (M + 1) 1-6 CF.sub.3 H H H Cl Q8 482 (M + 1) 1-7
CF.sub.3 H H H Cl Q9 450 (M + 1) 1-8 CF.sub.3 H H H Cl Q10 456 (M +
1) 1-9 CF.sub.3 H H H Cl Q11 490 (M + 1) 1-10 CF.sub.3 H H H Cl Q12
470 (M + 1) 1-11 CF.sub.3 H H H Cl Q13 470 (M + 1) 1-12 CF.sub.3 H
H H Cl Q14 466 (M + 1) 1-13 CF.sub.3 H H H Cl Q15 471 (M + 1) 1-14
CF.sub.3 H H H Cl Q16 472 (M + 1) 1-15 CF.sub.3 H H H Cl Q17 477 (M
+ 1) 1-16 CF.sub.3 H H H Cl Q18 511 (M + 1) 1-17 CF.sub.3 H H H Cl
Q19 461 (M + 1) 1-18 CF.sub.3 H H H Cl PhO 420 (M + 1) 1-19
CF.sub.3 H H H Cl 4-CF.sub.3--PhO 488 (M + 1) 1-20 I H H H Cl Q1
581 (M + 1) 1-21 I H H H Cl Q2 547 (M + 1) 1-22 I H H H Cl Q3 547
(M + 1) 1-23 I H H H Cl Q4 593 (M + 1) 1-24 I H H H Cl Q5 548 (M +
1) 1-25 I H H H Cl Q6 514 (M + 1) 1-26 I H H H Cl Q7 480 (M + 1)
1-27 I H H H Cl Q8 540 (M + 1) 1-28 I H H H Cl Q9 508 (M + 1) 1-29
I H H H Cl Q10 514 (M + 1) 1-30 I H H H Cl Q11 550 (M + 1) 1-31 I H
H H Cl Q12 528 (M + 1) 1-32 I H H H Cl Q13 528 (M + 1) 1-33 I H H H
Cl Q14 524 (M + 1) 1-34 I H H H Cl Q15 529 (M + 1) 1-35 I H H H Cl
Q16 530 (M + 1) 1-36 I H H H Cl Q17 535 (M + 1) 1-37 I H H H Cl Q18
569 (M + 1) 1-38 I H H H Cl Q19 519 (M + 1) 1-39 I H H H Cl PhO 478
(M + 1) 1-40 I H H H Cl 4-CF.sub.3--PhO 546 (M + 1) 1-41 CF.sub.3 H
Me H Cl Q1 537 (M + 1) 1-42 CF.sub.3 H Me H Cl Q2 503 (M + 1) 1-43
CF.sub.3 H Me H Cl Q3 503 (M + 1) 1-44 CF.sub.3 H Me Me Cl Q1 551
(M + 1) 1-45 CF.sub.3 H Me Me Cl Q2 517 (M + 1) 1-46 CF.sub.3 H Me
Me Cl Q3 517 (M + 1) 1-47 CF.sub.3 H CH.sub.2CH.sub.2 Cl Q1 549 (M
+ 1) 1-48 CF.sub.3 H CH.sub.2CH.sub.2 Cl Q2 515 (M + 1) 1-49
CF.sub.3 H CH.sub.2CH.sub.2 Cl Q3 515 (M + 1) 1-50 CF.sub.3 H H H
Cl 4-CF.sub.3--Ph 472 (M + 1) 1-51 CF.sub.3 H H H Cl 3-CF.sub.3--Ph
472 (M + 1) 1-52 CF.sub.3 H H H Cl 3,5-F.sub.2--Ph 440 (M + 1) 1-53
CF.sub.3 H H H Cl 4-MeO--Ph 434 (M + 1) 1-54 CF.sub.3 H H H Cl Ph
404 (M + 1) 1-55 CF.sub.3 H H H Cl 4-Py 405 (M + 1) 1-56 CF.sub.3 H
H H Cl 3-Py 405 (M + 1) 1-57 CF.sub.3 H Me H Cl 4-CF.sub.3--Ph 486
(M + 1) 1-58 CF.sub.3 H Me H Cl Ph 418 (M + 1) 1-59 CF.sub.3 H Me H
Cl 4-Py 419 (M + 1) 1-60 CF.sub.3 H MeO H Cl Q1 553 (M + 1) 1-61
CF.sub.3 H MeO H Cl Q2 519 (M + 1) 1-62 CF.sub.3 H MeO H Cl Q3 521
(M + 1) 1-63 CF.sub.3 H MeO H Cl Q17 507 (M + 1) 1-64 CF.sub.3 H
MeO H Cl PhO 418 (-MeOH) 1-65 CF.sub.3 H MeO H Cl 4-CF.sub.3--PhO
518 (M + 1) 1-66 CF.sub.3 H MeO H Cl 4-MeO--Ph 448 (-MeOH) 1-67
CF.sub.3 H MeO H Cl 3-PyO 451 (M + 1) 1-68 F F Me H Cl Q1 505 (M +
1) 1-69 F F Me H Cl Q2 471 (M + 1) 1-70 F F Me H Cl Q3 471 (M + 1)
1-71 F F Me Me Cl Q1 519 (M + 1) 1-72 F F Me Me Cl Q2 485 (M + 1)
1-73 F F Me Me Cl Q3 485 (M + 1) 1-74 F F CH.sub.2CH.sub.2 Cl Q3
517 (M + 1) 1-75 F F CH.sub.2CH.sub.2 Cl Q2 483 (M + 1) 1-76 F F
CH.sub.2CH.sub.2 Cl Q3 483 (M + 1) 1-77 CF.sub.3 H Me Me Me Q1 531
(M + 1) 1-78 CF.sub.3 H Me Me Me Q2 497 (M + 1) 1-79 I H Me Me Me
Q1 589 (M + 1) 1-80 F F Me Me Me Q1 499 (M + 1) In Table 1,
R.sup.1, R.sup.2, Y.sup.2 and Y.sup.4 represent H, and A represents
CH.
##STR00006##
TABLE-US-00002 TABLE 2 Compound Physical No. X.sup.1 R.sup.3
R.sup.4 Y.sup.1 Y.sup.3 property 2-1 CF.sub.3 H H Cl Ph 405 (M + 1)
2-2 CF.sub.3 H H Cl 4-CF.sub.3--Ph 473 (M + 1) 2-3 CF.sub.3 H H Cl
3-CF.sub.3--Ph 473 (M + 1) 2-4 CF.sub.3 H H Cl 3,5-F.sub.2--Ph 441
(M + 1) 2-5 CF.sub.3 H H Cl 4-MeO--Ph 435 (M + 1) 2-6 CF.sub.3 H H
Cl 4-Py 406 (M + 1) 2-7 CF.sub.3 H H Cl 3-Py 406 (M + 1) 2-8
CF.sub.3 Me H Cl Ph 419 (M + 1) 2-9 CF.sub.3 Me H Cl 4-CF.sub.3--Ph
487 (M + 1) 2-10 CF.sub.3 Me H Cl 3-CF.sub.3--Ph 487 (M + 1) 2-11
CF.sub.3 Me H Cl 3,5-F.sub.2--Ph 455 (M + 1) 2-12 CF.sub.3 Me Me Cl
Ph 433 (M + 1) 2-13 CF.sub.3 Me Me Cl 4-CF.sub.3--Ph 501 (M + 1)
2-14 CF.sub.3 Me Me Cl 3-CF.sub.3--Ph 501 (M + 1) 2-15 CF.sub.3 Me
Me Cl 3,5-F.sub.2--Ph 469 (M + 1) 2-16 I H H Cl Ph 463 (M + 1) 2-17
I H H Cl 4-CF.sub.3--Ph 531 (M + 1) 2-18 I H H Cl 3-CF.sub.3--Ph
531 (M + 1) 2-19 I H H Cl 3,5-F.sub.2--Ph 499 (M + 1) 2-20 I H H Cl
4-MeO--Ph 493 (M + 1) 2-21 I H H Cl 4-Py 464 (M + 1) 2-22 I H H Cl
3-Py 464 (M + 1) 2-23 I Me H Cl Ph 477 (M + 1) 2-24 I Me H Cl
4-CF.sub.3--Ph 2-25 I Me H Cl 3-CF.sub.3--Ph 2-26 I Me H Cl
3,5-F.sub.2--Ph 2-27 I Me Me Cl Ph 2-28 I Me Me Cl 4-CF.sub.3--Ph
2-29 I Me Me Cl 3-CF.sub.3--Ph 2-30 I Me Me Cl 3,5-F.sub.2--Ph In
Table 2 X.sup.2, R.sup.1, R.sup.2, Y.sup.2 and Y.sup.4 represent H,
and A represents a nitrogen atom.
[0265] The endoparasite control agent of the present invention has
excellent anti-endoparasite effect, and exerts appropriate control
effect against endoparasites. The animal for which the endoparasite
control agent of the present invention can be used is a human and
an animal of non-human mammalian or avian species. Exemplary
members of the non-human mammalian species include domestic
animals, such as pigs, horses, cattle, sheep, goats, rabbits,
camels, water buffalos, deer, mink and chinchillas; pet animals,
such as dogs, cats, little birds and monkeys; and experimental
animals, such as rats, mice, golden hamsters and guinea pigs.
Exemplary members of the avian species include domestic fowls, such
as chickens, ducks, aigamo ducks (crossbreeds of wild and domestic
ducks), quails, domestic ducks, geese and turkeys. The examples
listed above are non-limiting examples.
[0266] Human endoparasites against which the endoparasite control
agent of the present invention is effective are roughly classified
into protozoa and helminths. Examples of the protozoa include, but
are not limited thereto, Rhizopoda, such as Entamoeba histolytica;
Mastigophora, such as Leishmania, Trypanosoma and Trichomonas;
Sporozoea, such as Plasmodium and Toxoplasma; and Ciliophora, such
as Balantidium coli. Examples of the helminths include, but are not
limited thereto, Nematoda, such as Ascaris lumbricoides, Anisakis,
Toxocara canis, Trichostrongylus spp., Enterobius vemicularis,
hookworms (for example, Ancylostoma duodenale, Necator americanus,
Ancylostoma braziliense, etc.), Angiostrongylus spp., Gnathostoma
spp., filarial worms (filaria, Wuchereria bancrofti, Brugia malayi,
etc.), Onchocerca volvulus, Dracunculus medinensis, Trichinella
spiralis and Strongyloides stercoralis; Acanthocephala, such as
Macracanthorhynchus hirudinaceus; Gordiacea, such as Gordioidea;
Hirudinea, such as Hirudo nipponia; Trematoda, such as Schistosoma
japonicum, Schistosoma mansoni, Schistosoma haematobium, Clonorchis
sinensis, Heterophyes heterophyes, Fasciola spp. and Paragonimus
spp.; and Cestoda, such as Diphyllobothrium latum, Sparganum
mansoni, Sparganum proliferum, Diplogonoporus grandis, Taeniidae
for example, Taeniarhynchus saginatus, Taenia solium, Echinococcus,
etc.), Hymenolepis spp., Dipylidium caninum, Mesocestoides
lineatus, Bertiella spp. and Nybelinia surmenicola.
[0267] Non-human mammalian or avian endoparasites against which the
endoparasite control agent of the present invention is effective
are roughly classified into protozoa and helminths. Examples of the
protozoa include, hut are not limited thereto, Apicomplexa, such as
Cocoidia (for example, Eimeria, Isospora, Toxoplasma, Neospora,
Sarcocystis, Besnoitia, Hammondia, Cryptosporidium, Caryospora,
etc.), Haemosporina (for example, Leucocytozoon, Plasmodium, etc.),
Piroplasma (for example, Theileria, Anaplasma, Eperythrozoon,
Haemobartonella, Ehrlichia, etc.), and others (for example,
Hepatozoon, Haemogregarina, etc.); Microspora, such as
Encephalitozoon and Nosema; Mastigophora, such as Trypanosomatid
(for example, Trypanosoma, Leishmania, etc.), Trichomonadida (for
example, Chilomastix, Trichomonas, Monocercomonas, Histomonas,
etc.), and Diplomonadida (for example, Hexamita, Giardia, etc.);
Sarcodina, such as Amoebida (for example, Entamoeba histolytica
(Entamoeba) etc.); and Ciliophora, such as Balantidium coli
(Balantidium), Buxtonella and Entodinium.
[0268] Examples of the helminths include, but are not limited
thereto, Nentatoda, such as Ascaridida (for example, Ascaris suum
(Ascaris), Toxocara canis and Toxocara cati (Toxocara), Toxascaris
leonina (Toxascaris), Parascaris equorum (Parascaris), Ascaridia
galli (Ascaridia), Heterakis gallinarum (Heterakis), Anisakis,
etc.), Oxyurida (for example, Oxyuris equi (Qxyuris), Passalurus
ambiguus (Passalurus, etc.), Strongylida (for example, Strongylus
vulgaris (Strongylus), Haemonchus contortus (Haemonchus),
Ostertagia ostertagi (Ostertagia), Trichostrongylus colubriformis
(Trichostrongylus), Cooperia punctata (Cooperia), Nematodirus
filicollis (Nematodirus),Hyostrongylus rubidus (Hyostrongylus),
Oesophagostomum radiatum (Oesophagostomum) Chabertia ovina
(Chabertia), Ancylostoma caninum (Ancylostoma), Uncinaria
stenocephala (Uncinaria), Necator americanus (Necator), Bunostomum
phlebotomum (Bunostomum), Dictyocaulus viviparus (Dictyocaulas),
Metastrongylus elongatus (Metastrongylus), Filaroides hirthi
(Filaroides), Aelurostrongylus abstrusus (Aelurostrongylus),
Angiostrongylus cantonensis (Angiostrongylus), Syngamus trachea
(Syngamus), Stephanurus dentatus (Stephanurus), etc.), Rhabditida
(for example, Strongyloides stercoralis (Strongyloides), Micronema,
etc.), Spirurida (for example, Thelazia rhodesi (Thelazia),
Oxyspirura mansoni (Oxyspirura), Spirocerca lupi (Spirocerca),
Gongylonema pulchrum (Gongylonema), Draschia megastoma (Draschia),
Habronema microstoma (Habronema), Ascarops strongylina(Ascarops),
Physaloptera praeputialis (Physaloptera), Gnathostoma spinigerm
(Gnathostoma), etc.), Filariida (for example, Dirofilaria immitis
(Dirofilaria) Setaria equina (Setaria), Dipetalonema, Parafilaria
multipapillosa (Parafilaria), Onchocerca cervicalis (Onchocerca),
etc.), and Enoplida (for example, Parafilaria bovicola
(Parafilaria), Stephanofilaria okinawaensis (Stephanofilaria),
Trichuris vulpis (Trichuris), Capillaria bovis (Capillaria)
Trichosomoides crassicauda (Trichosomoides), Trichinella spiralis
(Trichinella), Dioctophyma renale (Dioctophyma), etc.); Trematoda,
such as Fasciolata (for example, Fasciola hepatica (Fasciola),
Fasciolopsis buski (Fasciolopsis), etc.), Paramphistomatidae (for
example, Homalogaster paloniae (Homalogaster), etc.), Dicrocoelata
(for example, Eurytrema pancreaticum (Eurytrema), Dicrocoelium
dendriticum (Dicrocoelium), etc.), Diplostomata (for example,
Pharyngostomum cordatum (Pharyngostomum), Alaria, etc.),
Echinostomata (for example, Echinostoma hortense (Echinostoma),
Echinochasmus, etc.), Troglotrematoidea (for example, lung flukes
(Paragonimus), Nanophyetus salmincola (Nanophyetus), etc.),
Opisthorchiida (for example, Clonorchis sinensis (Clonorchis)
etc.), Heterophyida (for example, Heterophyes heterophyes
(Heterophyes), Metagonimus yokogawai (Metagonimus), etc.),
Plagiorchiida (for example, Prosthogonimus ovatus (Prosthogonimus)
etc.), and Schistosomatidae (for example, Schistosoma japonicum
(Schistosoma) etc.); Cestoda, such as Pseudophylidea (for example,
Diphyllobothrium nihonkaiense (Diphyllobothrium), Spirometra
erinacei (Spirometra), etc.), and Cyclophyilldea (for example,
Anoplocephala perfoliata (Anoplocephala), Paranoplocephala
mamillana (Paranoplocephala), Moniezia benedeni (Moniezia),
Dipylidium caninum (Dipylidium), Mesocestoides lineatus
(Mesocestoides), Taenia pisiformis and Taenia hydatigena (Taenia),
Hydatigera taeniaeformis (Hydatigera), Multiceps multiceps
(Multiceps), Echinococcus granulosus (Echinococcus), Echinococcus
multilocularis (Echinococcus), Taenia solium (Taenia),
Taeniarhynchus saginatus (Taeniarhynchus), Hymenolepis diminuta
(Hymenolepis), Vampirolepis nana (Vampirolepis), Raillietina
tetragona (Raillietina), Amoebotaenia sphenoides (Amoebotaenia),
etc,); Acanthocephala, such as Macracanthorhynchus hirudinaceus
(Macracanthorhynchus) and Moniliformis moniliformis (Moniliformis);
Linguatulida, such as Linguatula serrata (Linguatula); and other
various parasites.
[0269] In different designations, examples of the helminths
include, but are not limited to, Nematoda, such as Enoplida (for
example, Trichuris spp., Capillaria spp., Trichomosoides spp.,
Trichinella spp., etc.), Rhabditia (for example, Micronema spp.,
Strongyloides spp., etc.), Strongylida (for example, Strongylus
spp., Triodontophorus spp., Oesophagodontus spp., Trichonema spp.,
Gyalocephalus spp., Cylindropharynx spp., Poteriostomum spp.,
Cyclococercus spp., Cylicostephanus spp., Oesophagostomum spp.,
Chabertia spp., Stephanurus spp., Ancylostoma spp., Uncinaria spp.,
Bunostomum spp., Globocephalus spp., Syngamus spp., Cyathostoma
spp., Metastrongylus spp., Dictyocaulus spp., Muellerius spp.,
Protostrongylus spp., Neostrongylus spp., Cystocaulus spp.,
Pneumostrongylus spp., Spicocaulus spp., Elaphostrongylus spp.,
Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp.,
Angiostrongylus spp., Aelurostrongylus spp., Filaroides, spp.,
Parafilaroides spp., Trichostrongylus spp., Haemonchus spp.,
Ostertagia spp., Marshallagia spp., Cooperia spp., Nematodirus
spp., Hyostrongylus spp., Obelisoides spp., Amidostomum spp.,
Ollulanus spp., etc.), Oxyurida (for example, Oxyuris spp.,
Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp.,
Heterakis spp., etc.), Ascaridia (for example, Ascaris spp.,
Toxascaris spp., Toxocara spp., Parascaris spp., Anisakis spp.,
Ascaridia spp., etc.), Spirurida (for example, Gnathostoma spp.,
Pyysaloptera spp., Thelazia spp., Gongylonema spp., Habronema spp.,
Parabronema spp., Draschia spp., Dracunculus spp., etc.), and
Filariida (for example, Stephanofilaria spp., Parafilaria spp.,
Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia
spp., Wuchereria spp., Onchocerca spp., etc.); Acanthocephala (for
example, Filicollis spp.. Moniliformis spp., Macracanthorhynchus
spp., Prosthenorchis spp., etc.); Trematoda including subclasses,
such as Monogenea (for example, Gyrodactylus spp., Dactylogyrus
spp., Polystoma spp., etc.) and Digenea (for example, Diplostomum
spp., Posthodiplostomum spp., Schistosoma spp., Trichobilharzia
spp., Ornithbilharzia spp., Austrobilharzia spp., Gigantobilharzia
spp., Leucochloridium spp., Brachylaima spp., Echinostoma spp.,
Echinoparyphium spp., Echinochasmus spp., Hypoderaeum spp.,
Fasciola spp., Fasciolides spp., Fasciolopsis spp., Cyclocoelum
spp., Typhlocoelum spp., Paramphistomum spp., Calicophoron spp.,
Cotylophoron spp., Gigantcotyle spp., Fischoederius spp.,
Gastrothylacus spp., Notocotylus spp., Catatropis spp., Plagiorchis
spp., Prosthogonimus spp., Dicrocoelium spp., Eurytrema spp.,
Troglatrema spp., Paragonimus spp., Collyriclum spp., Nanophyetus
spp., Opisthorchis spp., Clonorchis spp., Metorchis spp.,
Heterophyes spp., Metagonimus spp., etc.);
[0270] Cestoda, such as Pseudophyllidea (for example,
Diphyllobothrium spp., Spirometra spp., Schistocephalus spp.,
Ligula spp., Bothridium spp., Diplogonoporus spp., etc.), and
Cyclophyllidea (for example, Mesocestoides spp., Anoplocephala
spp., Paranoplocehala spp., Moniezia spp., Thysanosomsa spp.,
Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp.,
Andyra spp., Bertiella spp., Taenia spp., Echinococcus spp.,
Hydatigera spp., Davainea spp., Raillietina spp., Hymenolepis spp.,
Echinolepis spp., Echinocotyle spp., Diorchis spp., Dipylidium
spp., Joyeuxiella spp., Diplopylidium spp., etc.); and others
including parasites belonging to Acanthocephala and
Linguatulida.
[0271] The endoparasite control agent of the present invention is
effective for controlling not only parasites that live in the body
of an intermediate or final host, but also parasites that live in
the body of a reservoir host. The compound represented by the
general formula (I) of the present invention is effective for
controlling parasites at their every developmental stage. For
example, in the case of protozoa, the compound is effective against
their cysts, precystic forms and trophozoites; schizonts and
amoeboid forms at the asexual stage; gametocytes, gametes and
zygotes at the sexual stage; sporozoites; etc. In the case of
nematodes, the compound is effective against their eggs, larvae and
adults. The compound of the present invention is capable of not
only disinfecting parasites in the living body, but also even
preventing parasitic infection by application to the environment as
a route of infection. For example, soil-borne infection, i.e.,
infection from soil of crop fields and parks; percutaneous
infection from water in rivers, lakes, marshes, paddy fields, etc.;
oral infection from feces of animals such as dogs and cats; oral
infection from saltwater fish, freshwater fish, crustaceans,
shellfish, raw meat of domestic animals, etc.; infection from
mosquitoes, gadflies, flies, cockroaches, mites and ticks, fleas,
lice, assassin bugs, trombiculid mites, etc.; and the like can be
prevented from occurring.
[0272] The endoparasite control agent of the present invention can
be administered as a pharmaceutical for treatment or prevention of
parasitosis in humans and animals of non-human mammalian or avian
species. The mode of administration may be oral or parenteral
administration. In the case of oral administration, the
endoparasite control agent of the present invention can be
administered, for example, as a capsule, a tablet, a pill, a
powder, a granule, a fine granule, a powder, a syrup, an
enteric-coated preparation, a suspension or a paste, or after
blended in a liquid drink or feed for animals. In the case of
parenteral administration, the endoparasite control agent of the
present invention can be administored, for example, as an
injection, an infusion, a suppository, an emulsion, a suspension, a
drop, an ointment, a cream, a solution, a lotion, a spray, an
aerosol, a cataplasm or a tape, or in a dosage form which allows
sustained mucosal or percutaneous absorption.
[0273] In the case where the endoparasite control agent of the
present invention is used as a pharmaceutical for humans and
animals of non-human mammalian or avian species, the optimum amount
(effective amount) of the active ingredient varies with the purpose
(treatment or prevention), the kind of infectious parasite, the
type and severity of infection, the dosage form, etc., but in
general, the oral daily dose is in the range of about 0.0001 to
10000 mg/kg body weight and the parenteral daily dose is in the
range of about 0.0001 to 10000 mg/kg body weight. Such a dose may
be given as a single dose or divided into multiple doses.
[0274] The concentration of the active ingredient in the
endoparasite control agent of the present invention is generally
about 0.001 to 100% by mass, preferably about 0.001 to 99% by mass,
and more preferably about 0.005 to 20% by mass. The endoparasite
control agent of the present invention may be a composition that
can be directly administered, or a highly concentrated composition
that needs to be diluted to a suitable concentration before
use.
[0275] The endoparasite control agent of the present invention can
be used in combination with any existing endoparasite control agent
for the purpose of reinforcing or complementing its effect. In such
a combined use, two or more active ingredients may be mixed and
formulated into a single preparation before administration, or two
or more different preparations may be administered separately.
EXAMPLES
[0276] Next, the present invention will be illustrated in detail by
formulation examples and test example of the endoparasite control
agent of the present invention, but the scope of the present
invention is not limited by the following formulation examples and
test example.
[0277] In Examples, "part" means a part by mass.
Formulation Example 1
Emulsion
[0278] Ten parts of a carboxamide derivative represented by the
general formula (I) of the present invention, 6 parts of Sorpol
355S (surfactant, manufactured by Toho Chemical Industry), and 84
parts of Solvesso 150 (manufactured by Exxon) are uniformly mixed
with stirring to give an emulsion.
Formulation Example 2
Ointment
[0279] One part of a carboxamide derivative represented by the
general formula (I) of the present invention, 50 parts of white
beeswax, and 43 parts of white petrolatum are well mixed to give an
ointment.
Formulation Example 3
Tablet
[0280] Two parts of a carboxamide derivative represented by the
general formula (I) of the present invention, 10 parts of vegetable
oil (olive oil), 3 parts of crystalline cellulose, 20 parts of
white carbon, and 65 parts of kaolin are well mixed and compressed
into a tablet.
Formulation Example 4
Injection
[0281] Ten parts of a carboxamide derivative represented by the
general formula (I) of the present invention, 10 parts of propylene
glycol for use as a food additive, and 80 parts of vegetable oil
(corn oil) are mixed to give an injection.
Formulation Example 5
Solution
[0282] Five parts of a carboxamide derivative represented by the
general formula (I) of the present invention, 20 parts of a
surfactant for ordinary use as a dissolution or suspension aid, and
75 parts of ion exchanged water are well mixed to give a
solution.
Test Example
Test for Effect on Motion of Larvae of Haemonchus Nematode
(Haemonchus contortus)
[0283] The compound of the present invention was prepared as
solutions in 100% DMSO at the final concentrations of 50 ppm, 5
ppm, 0.5 ppm, 0.05 ppm and 0.005ppm. DMSO stands for dimethyl
sulfoxide.
[0284] A larval suspension containing 1st-stage larvae of
Haemonchus contortus harvested by the Baermann technique (for
example, see K. Nakazono et al., "Inclination of Baermann funnel
wall and efficiency of nematode extraction" Proc. Assoc. Pl. Prot.
Kyushu 33: 126-130 (1987)) was placed at a density of 20 larvae per
well in a test plate, and 0.5 .mu.L/well of the test solution
containing the compound of the present invention diluted to a
predetermined concentration was added to the test plate. The plate
was kept under the conditions of 27.degree. C./95% RH for 4 days.
In the test, ivermectin was used for the positive control and DMSO
was used for the negative control.
[0285] The motor ability of the larvae was examined with an
automatic analyzer equipped with an LCD camera. The inhibitory
effect on the motion of the larvae in each treatment plot was
corrected based on the inhibitory effect in the plot treated with
DMSO only for the negative control. The EC.sub.50 value was
calculated from the data on the corrected inhibitory effect on the
motion of the larvae, and graded according to the criteria shown
below.
[0286] The test was conducted in duplicate per plot.
Grading Criteria
[0287] EC.sub.50 value:
TABLE-US-00003 0.05 ppm or less A 0.05 to 1 ppm B 1 to 10 ppm C 10
ppm or more D
[0288] As a result, the compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-6,
1-7, 1-8, 1-9, 1-10, 1-11, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18,
1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29,
1-30, 1-31, 1-32, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41,
1-42, 1-43, 1-44, 1-45, 1-45, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52,
1-53, 1-54, 1-55, 1-56, 1-57,1-58, 1-59, 1-60, 1-61, 1-62, 1-63,
1-64, 1-65, 1-66, 1-67, 2-1, 2-2, 2-3, 2-4 and 2-5 of the present
invention showed the activity level graded as C or higher.
[0289] The results show that the compounds of the present invention
are effective as an endoparasite control agent.
* * * * *