Heterocyclic Compounds And Their Use As Glycogen Synthase Kinase-3 Inhibitors

Abstract

The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

Description

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This claims priority to U.S. Provisional Patent Application No. 61/386,849, filed on Sep. 27, 2010, the contents of which are hereby incorporated by reference.

TECHNICAL FIELD

[0002] The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

BACKGROUND OF THE INVENTION

[0003] Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase encoded by two isoforms, GSK-3.alpha. and GSK-3.beta., with molecular weights of 51 and 47 kDa, respectively. These share 97% sequence similarity in their kinase catalytic domains. The GSK-3.alpha. isoform has an extended glycine-rich N-terminal tail. A minor splice variant of GSK-3.beta. has been identified (expressed at .about.15% of total) with a 13 amino acid insert within the kinase domain. This variant had a reduced activity towards tau. GSK-3 is highly conserved throughout evolution, and found in all mammalians thus far with high homology in the kinase domain. Both isoforms are ubiquitously expressed in mammalian tissues, including the brain. Pharmacological GSK-3 inhibitors are not able to selectively inhibit one of the isoforms.

[0004] GSK-3.beta. plays an important role in the control of metabolism, differentiation and survival. It was initially identified as an enzyme able to phosphorylate and hence inhibit glycogen synthase. Subsequently, it was recognised that GSK-3.beta. was identical to tau protein kinase 1 (TPK1), an enzyme that phosphorylates tau protein in epitopes that are also found to be hyperphosphorylated in Alzheimer's disease and in several tauopathies.

[0005] Interestingly, protein kinase B (AKT) phosphorylation of GSK-3.beta. results in a loss of kinase activity, and it has been proposed that this inhibition may mediate some of the effects of neurotrophic factors. Moreover, phosphorylation of .beta.-catenin (a protein involved in cell survival) by GSK-3.beta., results in its degradation by an ubiquitinilation dependent proteasome pathway.

[0006] Therefore it appears that inhibition of GSK-3.beta. activity may result in neurotrophic activity. There is evidence that lithium, an uncompetitive inhibitor of GSK-3.beta., enhances neuritogenesis in some models and can also increase neuronal survival, through the induction of survival factors such as Bcl-2 and the inhibition of the expression of proapoptotic factors such as P53 and Bax.

[0007] Further studies have shown that .beta.-amyloid increases GSK-3.beta. activity and tau protein phosphorylation. Moreover, this hyperphosphorylation as well as the neurotoxic effects of .beta.-amyloid are blocked by lithium chloride and by a GSK-3.beta. antisense mRNA. These observations taken together suggest that GSK-3.beta. may be the link between the two major pathological processes in Alzheimer's disease: abnormal APP (Amyloid Precursor Protein) processing and tau protein hyperphosphorylation.

[0008] These experimental observations indicate that compounds which modulate the GSK-3.beta. activity may find application in the treatment of the neuropathological consequences and the cognitive and attention deficits associated with Alzheimer's disease, as well as other acute and chronic neurodegenerative diseases. These include, but are not limited to: Parkinson's disease, tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy, argyophilic grain disease) and other dementia including vascular dementia; acute stroke and others traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration); brain and spinal cord trauma; peripheral neuropathies; bipolar disorders, retinopathies and glaucoma.

[0009] GSK-3.beta. may further have utility in the treatment of inflammatory diseases, such as rheumatoid arthritis and osteoarthritis.

[0010] GSK-3.beta. may also have utility in the treatment of other diseases such as: Non-insulin dependent diabetes and obesity; osteoporosis; manic depressive illness; schizophrenia; alopecia; cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus-induced tumors.

[0011] A review on GSK-3, its functions, its therapeutic potential and its possible inhibitors is given in "Glycogen Synthase Kinase 3 (GSK-3) and its inhibitors: Drug Discovery and Developments" by A. Martinez et al. (editors), John Wiley and Sons, 2006.

[0012] WO 03/053330 describes 2-oxindoles substituted in the 3-position with a bicyclic hetaryl group and their use for treating conditions related to glycogen synthase kinase-3. WO 03/082853 describes substituted 2-oxindoles substituted in the 3-position with a monocyclic hetaryl group and their use for treating conditions related to glycogen synthase kinase-3. WO 2005/123672 relates to 2-hydroxyindoles carrying in the 3-position an optionally fused pyrid-2-yl ring and their use for inhibiting kinases. WO 2005/061519 relates to 2-hydroxyindoles carrying in the 3-position a pyrid-2-yl ring fused to an aromatic or heteroaromatic ring and their use for inhibiting kinases.

SUMMARY OF THE INVENTION

[0013] The object of the present invention is to provide compounds which modulate the GSK-3.beta. activity, in particular compounds which have an inhibitory activity on GSK-3.beta. and which thus are useful as an active ingredient of a composition for preventive and/or therapeutic treatment of a disease caused by abnormal GSK-3.beta. activity, especially of neurodegenerative and/or inflammatory diseases. More specifically, the goal is to provide novel compounds useful as an active ingredient of a composition that enables prevention and/or treatment of neurodegenerative diseases such as Alzheimer's disease.

[0014] It was surprisingly found that the problem is solved by providing a heterocyclic compound of the general formulae IA and IB

##STR00001##

the stereoisomers, N-oxides, prodrugs, tautomers and/or physiologically tolerated acid addition salts thereof; and the compounds of the general formulae IA and IB, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, wherein [0015] X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are independently of each other selected from the group consisting of CR.sup.1 and N; [0016] each R.sup.1 is independently selected from the group consisting of hydrogen, cyano, NR.sup.aR.sup.b, OH, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, formyl, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, COOH, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, C.sub.1-C.sub.6-alkyl-NR.sup.aR.sup.b, CO--NR.sup.aR.sup.b, an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising 1, 2 or 3 heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R.sup.7 and wherein Ar may also be bonded via a CH.sub.2 group, and saturated or partially unsaturated 3-, 4-, 5-, 6- or 7-membered heterocyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein the heterocyclic radical is unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0017] R.sup.2 is hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, OH or F; [0018] R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1, 2 or 3 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O, S, SO, SO.sub.2, NR.sup.c and NO, and where 1, 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8; [0019] where the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are independently selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and NR.sup.aR.sup.b; [0020] each R.sup.7 is independently selected from the group consisting of halogen, OH, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, CO--NR.sup.aR.sup.b, a phenyl group and a saturated, partially unsaturated or aromatic 5- or 6-membered heterocyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein phenyl and the heterocyclic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, or in the heterocyclic ring two geminally bound radicals may together form a group .dbd.O; [0021] each R.sup.8 is independently selected from the group consisting of halogen, OH, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, CO--NR.sup.aR.sup.b, a phenyl group and a saturated, partially unsaturated or aromatic 3-, 4-, 5-, 6- or 7-membered hetero-cyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein phenyl and the heterocyclic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; [0022] R.sup.a and R.sup.b are independently of each other selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl; or [0023] R.sup.a and R.sup.b form, together with the nitrogen atom to which they are bonded, a 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom-containing group selected from N, O, S, SO and SO.sub.2 as a ring member, where the N-heterocyclic ring may carry 1 or 2 radicals selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; and [0024] each R.sup.c is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl.

[0025] Thus, the present invention relates to compounds of the formulae IA and IB as defined herein and in the claims, to the stereoisomers, tautomers, prodrugs and/or physiologically tolerated acid addition salts thereof.

[0026] According to a further aspect, the present invention relates to a pharmaceutical composition comprising at least one compound of the formula IA and/or IB as defined herein, a stereoisomer, a tautomer, a prodrug and/or a physiologically tolerated acid addition salt thereof or comprising at least one heterocyclic compound as defined above, wherein at least one of the atoms has been replaced by its stable, nonradioactive isotope, optionally together with at least one physiologically acceptable carrier and/or auxiliary substance.

[0027] According to a further aspect, the present invention relates to the use of at least one compound of the formula IA and/or IB as defined herein, the stereoisomers, tautomers, prodrugs and/or physiologically tolerated acid addition salts thereof, for the preparation of a medicament for the treatment of a medical disorder susceptible to treatment with a compound that modulates glycogen synthase kinase 3.beta. activity.

[0028] According to a further aspect, the present invention relates to a method for treating a medical disorder susceptible to treatment with a compound that modulates glycogen synthase kinase 3.beta. activity, said method comprising administering an effective amount of at least one compound of the formula IA and/or IB as defined herein, a stereoisomer, a tautomer, a prodrug and/or a physiologically tolerated acid addition salt thereof, to a subject in need thereof.

DETAILED DESCRIPTION OF THE INVENTION

[0029] Provided the compounds of the formulae IA and IB of a given constitution may exist in different spatial arrangements, for example if they possess one or more centers of asymmetry, polysubstituted rings or double bonds, or as different tautomers, it is also possible to use enantiomeric mixtures, in particular racemates, diastereomeric mixtures and tautomeric mixtures, preferably, however, the respective essentially pure enantiomers, diastereomers and tautomers of the compounds of formulae IA and IB and/or of their salts.

[0030] In case R.sup.2 in compound IB is hydrogen, this compound IB is a tautomer of the respective compound IA wherein the remaining variables have the same meaning.

[0031] It is likewise possible to use physiologically tolerated salts of the compounds of the formulae IA and/or IB, especially acid addition salts with physiologically tolerated acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, C.sub.1-C.sub.4-alkylsulfonic acids, such as methanesulfonic acid, aromatic sulfonic acids, such as benzenesulfonic acid and toluenesulfonic acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, adipic acid and benzoic acid. Other utilizable acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 et seq., Birkhauser Verlag, Basel and Stuttgart, 1966.

[0032] In the terms of the present invention, "prodrugs" are compounds which are metabolized in vivo to give the compounds of the invention of formulae IA or IB. Typical examples for prodrugs are for example decribed in C. G. Wermeth (editor): The Practice of Medicinal Chemistry, Academic Press, San Diego, 1996, pages 671-715. Examples are phosphates, carbamates, aminoacids, esters, amides, peptides, urea and the like. In the present case, suitable prodrugs can be compounds of formula IA or IB wherein an external nitrogen atom, for example a secondary nitrogen ring atom of the ring fused to the pyridyl ring (i.e. in the group --(CH.sub.2).sub.m-- formed by R.sup.3 together with R.sup.4 or R.sup.4 together with R.sup.5 or R.sup.5 together with R.sup.6, at least one CH.sub.2 group is replaced by a group NR.sup.c and at least one R.sup.c is hydrogen) or a nitrogen atom of a primary or secondary amino group being a substituent R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and/or R.sup.8 (=at least one of R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is NR.sup.aR.sup.b, wherein at least one of R.sup.a and R.sup.b is H), forms an amide/peptide bond in that this nitrogen atom is substituted by a C.sub.1-C.sub.4-alkylcarbonyl group, e.g. by acetyl, propionyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl or tertbutylcarbonyl (pivaloyl), by benzoyl, or by an aminoacid group bonded via CO, e.g. glycine, alanine, serine, phenylalanine and the like bonded via CO. Suitable prodrugs are furthermore alkylcarbonyloxyalkylcarbamates, wherein said nitrogen atom carries a group --C(.dbd.O)--O--CHR.sup.x--O--C(.dbd.O)--R.sup.y, wherein R.sup.x and R.sup.y independently of each other are C.sub.1-C.sub.4-alkyl. These carbamate compounds are for example described in J. Alexander, R. Cargill, S. R. Michelson, H. Schwam, J. Medicinal Chem. 1988, 31(2), 318-322. These groups can be removed under metabolic conditions and result in compounds IA/IB wherein said nitrogen atom carries a hydrogen atom instead. Also, R.sup.1 may be chosen so as to be hydrolysable under metabolic conditions and thus to be one of the above-listed groups (i.a. a C.sub.1-C.sub.4-alkylcarbonyl group, an aminoacid group bonded via CO or a group --C(.dbd.O)--O--CHR.sup.x--O--C(.dbd.O)--R.sup.y). Another prodrug is e.g. a compound IB, wherein R.sup.2 is F.

[0033] The compounds of formulae IA or IB may also be present in the form of the respective tautomers. Apart the tautomery already mentioned above of formulae IA and IB, where in formula IB R.sup.2 is H, tautomery may also be present in compounds IA and IB wherein R.sup.1 is OH and this substituent is bonded to a carbon atom which is in .alpha.-position to a nitrogen ring atom. This results for example in following tautomeric formulae (the examples are only given for formula IA, but are analogous for formula IB):

##STR00002##

[0034] The organic moieties mentioned in the above definitions of the variables are--like the term halogen--collective terms for individual listings of the individual group members. The prefix C.sub.n-C.sub.m indicates in each case the possible number of carbon atoms in the group.

[0035] The term halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

[0036] C.sub.1-C.sub.2-Alkyl is methyl or ethyl; C.sub.1-C.sub.3-alkyl is additionally n-propyl or isopropyl.

[0037] C.sub.1-C.sub.4-Alkyl is a straight-chain or branched alkyl group having from 1 to 4 carbon atoms. Examples are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl (sec-butyl), isobutyl and tert-butyl.

[0038] C.sub.1-C.sub.6-Alkyl is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms. Examples include the residues mentioned above for C.sub.1-C.sub.4-alkyl and also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.

[0039] C.sub.1-C.sub.2-Haloalkyl is an alkyl group having 1 or 2 carbon atoms (as mentioned above), where at least one of the hydrogen atoms, e.g. 1, 2, 3, 4 or 5 hydrogen atoms in these groups are replaced by halogen atoms as mentioned above, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl or pentafluoroethyl.

[0040] C.sub.1-C.sub.4-Haloalkyl is a straight-chain or branched alkyl group having 1 to 4 carbon atoms (as mentioned above), where at least one of the hydrogen atoms, e.g. 1, 2, 3, 4 or 5 hydrogen atoms in these groups are replaced by halogen atoms as mentioned above. Examples are, apart those listed above for C.sub.1-C.sub.2-haloalkyl, 1-chloropropyl, 1-bromopropyl, 1-fluoropropyl, 2-chloropropyl, 2-bromopropyl, 2-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 3-fluoropropyl, 1,1-dichloropropyl, 1,1-difluoropropyl, 2,2-dichloropropyl, 2,2-difluoropropyl, 2,3-dichloropropyl, 2,3-difluoropropyl, 1,3-dichloropropyl, 1,3-difluoropropyl, 3,3-dichloropropyl, 3,3-difluoropropyl, 1,1,2-trichloropropyl, 1,1,2-trifluoropropyl, 1,2,2-trichloropropyl, 1,2,2-trifluoropropyl, 1,2,3-trichloropropyl, 1,2,3-trifluoropropyl, 2,2,3-trichloropropyl, 2,2,3-trifluoropropyl, 3,3,3-trichloropropyl, 3,3,3-trifluoropropyl, 1,1,1-trifluoroprop-2-yl, 1-chlorobutyl, 1-bromobutyl, 1-fluorobutyl, 2-chlorobutyl, 2-bromobutyl, 2-fluorobutyl, 3-chlorobutyl, 3-bromobutyl, 3-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, 4-fluorobutyl, and the like.

[0041] C.sub.1-C.sub.6-Haloalkyl is a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as mentioned above), where at least one of the hydrogen atoms in these groups is replaced by halogen atoms as mentioned above. Examples are, apart those listed above for C.sub.1-C.sub.4-haloalkyl, chloropentyl, bromopentyl, fluoropentyl, chlorohexyl, bromohexyl, fluorohexyl, and the like.

[0042] C.sub.1-C.sub.2-Fluoroalkyl (=fluorinated C.sub.1-C.sub.2-alkyl) is an alkyl group having 1 or 2 carbon atoms (as mentioned above), where at least one of the hydrogen atoms, e.g. 1, 2, 3, 4 or 5 hydrogen atoms in these groups are replaced by fluorine atoms, such as difluoromethyl, trifluoromethyl, 1-fluoroethyl, (R)-1-fluoroethyl, (S)-1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, or pentafluoroethyl.

[0043] C.sub.1-C.sub.4-Fluoroalkyl (=fluorinated C.sub.1-C.sub.4-alkyl) is a straight-chain or branched alkyl group having 1 to 4 carbon atoms (as mentioned above), where at least one of the hydrogen atoms, e.g. 1, 2, 3, 4 or 5 hydrogen atoms in these groups are replaced by fluorine atoms. Examples are, apart those listed above for C.sub.1-C.sub.2-fluoroalkyl, 1-fluoropropyl, (R)-1-fluoropropyl, (S)-1-fluoropropyl, 2-fluoropropyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 1,2-difluoropropyl, 2,3-difluoropropyl, 1,3-difluoropropyl, 3,3-difluoropropyl, 1,1,2-trifluoropropyl, 1,2,2-trifluoropropyl, 1,2,3-trifluoropropyl, 2,2,3-trifluoropropyl, 3,3,3-trifluoropropyl, 1,1,1-trifluoroprop-2-yl, 2-fluoro-1-methylethyl, (R)-2-fluoro-1-methylethyl, (S)-2-fluoro-1-methylethyl, 2,2-difluoro-1-methylethyl, (R)-2,2-difluoro-1-methylethyl, (S)-2,2-difluoro-1-methylethyl, 1,2-difluoro-1-methylethyl, (R)-1,2-difluoro-1-methylethyl, (S)-1,2-difluoro-1-methylethyl, 2,2,2-trifluoro-1-methylethyl, (R)-2,2,2-trifluoro-1-methylethyl, (S)-2,2,2-trifluoro-1-methylethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, 1-(trifluoromethyl)-2,2,2-trifluoroethyl, 1-(trifluoromethyl)-1,2,2,2-tetrafluoroethyl, 1-fluorobutyl, (R)-1-fluorobutyl, (S)-1-fluorobutyl, 2-fluorobutyl, (R)-2-fluorobutyl, (S)-2-fluorobutyl, 3-fluorobutyl, (R)-3-fluorobutyl, (S)-3-fluorobutyl, 4-fluorobutyl, 1,1-difluorobutyl, 2,2-difluorobutyl, 3,3-difluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl and the like.

[0044] C.sub.1-C.sub.6-Fluoroalkyl (=fluorinated C.sub.1-C.sub.6-alkyl) is a straight-chain or branched alkyl group having 1 to 6 carbon atoms (as mentioned above), where at least one of the hydrogen atoms, e.g. 1, 2, 3, 4 or 5 hydrogen atoms in these groups are replaced by fluorine atoms. Examples are, apart those listed above for C.sub.1-C.sub.4-fluoroalkyl, 1-fluoropentyl, (R)-1-fluoropentyl, (S)-1-fluoropentyl, 2-fluoropentyl, (R)-2-fluoropentyl, (S)-2-fluoropentyl, 3-fluoropentyl, (R)-3-fluoropentyl, (S)-3-fluoropentyl, 4-fluoropentyl, (R)-4-fluoropentyl, (S)-4-fluoropentyl, 5-fluoropentyl, (R)-5-fluoropentyl, (S)-5-fluoropentyl, 1-fluorohexyl, (R)-1-fluorohexyl, (S)-1-fluorohexyl, 2-fluorohexyl, (R)-2-fluorohexyl, (S)-2-fluorohexyl, 3-fluorohexyl, (R)-3-fluorohexyl, (S)-3-fluorohexyl, 4-fluorohexyl, (R)-4-fluorohexyl, (S)-4-fluorohexyl, 5-fluorohexyl, (R)-5-fluorohexyl, (S)-5-fluorohexyl, 65-fluorohexyl, (R)-6-fluorohexyl, (S)-6-fluorohexyl, and the like.

[0045] C.sub.1-C.sub.4-Alkoxy is a straight-chain or branched alkyl group having from 1 to 4 carbon atoms, which is bound to the remainder of the molecule via an oxygen atom. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-butoxy, isobutoxy and tert-butoxy.

[0046] C.sub.1-C.sub.6-Alkoxy is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms, which is bound to the remainder of the molecule via an oxygen atom. Examples include, apart those listed above for C.sub.1-C.sub.4-alkoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutyloxy, 1,2-dimethylbutyloxy, 1,3-dimethylbutyloxy, 2,2-dimethylbutyloxy, 2,3-dimethylbutyloxy, 3,3-dimethylbutyloxy, 1-ethylbutyloxy, 2-ethylbutyloxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.

[0047] Halogenated C.sub.1-C.sub.6-alkoxy (which is also termed C.sub.1-C.sub.6-haloalkoxy), in particular fluorinated C.sub.1-C.sub.6-alkoxy (also termed C.sub.1-C.sub.6-fluoroalkoxy) is a straight-chain or branched alkoxy group having from 1 to 6, in particular 1 to 4 carbon atoms (=fluorinated C.sub.1-C.sub.4-alkoxy), wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a halogen atoms, in particular fluorine atoms such as in fluoromethoxy, difluoromethoxy, trifluoromethoxy, (R)-1-fluoroethoxy, (S)-1-fluoroethoxy, 2-fluoroethoxy, 1,1-difluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, (R)-1-fluoropropoxy, (S)-1-fluoropropoxy, (R)-2-fluoropropoxy, (S)-2-fluoropropoxy, 3-fluoropropoxy, 1,1-difluoropropoxy, 2,2-difluoropropoxy, 3,3-difluoropropoxy, 3,3,3-trifluoropropoxy, (R)-2-fluoro-1-methylethoxy, (S)-2-fluoro-1-methylethoxy, (R)-2,2-difluoro-1-methylethoxy, (S)-2,2-difluoro-1-methylethoxy, (R)-1,2-difluoro-1-methylethoxy, (S)-1,2-difluoro-1-methylethoxy, (R)-2,2,2-trifluoro-1-methylethoxy, (S)-2,2,2-trifluoro-1-methylethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, (R)-1-fluorobutoxy, (S)-1-fluorobutoxy, 2-fluorobutoxy, 3-fluorobutoxy, 4-fluorobutoxy, 1,1-difluorobutoxy, 2,2-difluorobutoxy, 3,3-difluorobutoxy, 4,4-difluorobutoxy, 4,4,4-trifluorobutoxy, and the like.

[0048] C.sub.1-C.sub.4-Alkylcarbonyl is a straight-chain or branched alkyl group having from 1 to 4 carbon atoms), which is bound to the remainder of the molecule via a carbonyl group (CO), such as in acetyl, propionyl, isopropylcarbonyl, butylcarbonyl, sec-butylcarbonyl, isobutylcarbonyl, and tert-butylcarbonyl.

[0049] C.sub.1-C.sub.6-Alkylcarbonyl is a straight-chain or branched alkyl group having from 1 to 6 carbon atoms, which is bound to the remainder of the molecule via a carbonyl group (CO). Examples include, apart those listed above for C.sub.1-C.sub.4-alkylcarbonyl, pentylcarbonyl, hexylcarbonyl and the constitutional isomers thereof.

[0050] C.sub.1-C.sub.4-Haloalkylcarbonyl is a straight-chain or branched haloalkyl group having from 1 to 4 carbon atoms as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO)

[0051] C.sub.1-C.sub.6-Haloalkylcarbonyl is a straight-chain or branched haloalkyl group having from 1 to 6 carbon atoms as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO)

[0052] C.sub.1-C.sub.4-Fluoroalkylcarbonyl is a straight-chain or branched fluoroalkyl group having from 1 to 4 carbon atoms as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO)

[0053] C.sub.1-C.sub.6-fluoroalkylcarbonyl is a straight-chain or branched fluoroalkyl group having from 1 to 6 carbon atoms as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO)

[0054] C.sub.1-C.sub.6-Alkoxycarbonyl is a straight-chain or branched alkoxy group having from 1 to 6, especially 1 to 4 carbon atoms (.dbd.C.sub.1-C.sub.4-alkoxycarbonyl), in particular 1 to 3 carbon atoms (.dbd.C.sub.1-C.sub.3-alkoxycarbonyl), which is bound to the remainder of the molecule via a carbonyl group (CO), such as in methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, and isopropyloxycarbonyl.

[0055] C.sub.1-C.sub.6-Haloalkoxycarbonyl is a straight-chain or branched haloalkoxy group having from 1 to 6, especially 1 to 4 carbon atoms (.dbd.C.sub.1-C.sub.4-haloalkoxycarbonyl), in particular 1 to 3 carbon atoms (.dbd.C.sub.1-C.sub.3-haloalkoxycarbonyl) as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO).

[0056] C.sub.1-C.sub.6-Fluoroalkoxycarbonyl is a straight-chain or branched fluorooalkoxy group having from 1 to 6, especially 1 to 4 carbon atoms (.dbd.C.sub.1-C.sub.4-fluoroalkoxycarbonyl), in particular 1 to 3 carbon atoms (.dbd.C.sub.1-C.sub.3-fluoroalkoxycarbonyl) as defined above, which is bound to the remainder of the molecule via a carbonyl group (CO).

[0057] C.sub.3-C.sub.6-Cycloalkyl is a cycloaliphatic radical having from 3 to 6 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. C.sub.3-C.sub.4-cycloalkyl is a cycloaliphatic radical having from 3 to 4 C atoms, such as cyclopropyl and cyclobutyl.

[0058] C.sub.3-C.sub.7-Cycloalkyl is a cycloaliphatic radical having from 3 to 7 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

[0059] C.sub.3-C.sub.6-Halocycloalkyl is a cycloaliphatic radical having from 3 to 6 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a halogen atoms, preferably by fluorine atoms such as in 1-fluorocyclopropyl, 2-fluorocyclopropyl, (S)- and (R)-2,2-difluorocyclopropyl, 1,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, pentafluorocyclopropyl, 1-fluorocyclobutyl, 2-fluorocyclobutyl, 3-fluorocyclobutyl, 2,2-difluorocyclobutyl, 3,3-difluorocyclobutyl, 1,2-difluorocyclobutyl, 1,3-difluorocyclobutyl, 2,3-difluorocyclobutyl, 2,4-difluorocyclobutyl, or 1,2,2-trifluorocyclobutyl.

[0060] C.sub.3-C.sub.7-Halocycloalkyl is a cycloaliphatic radical having from 3 to 7 C atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a halogen atoms, preferably by fluorine atoms. Examples include, apart those listed above for C.sub.3-C.sub.6-fluorocycloalkyl, 1-fluorocycloheptyl, 2-fluorocycloheptyl, 3-fluorocycloheptyl, 4-fluorocycloheptyl, 1,2-difluorocycloheptyl, 1,3-difluorocycloheptyl, 1,4-difluorocycloheptyl, 2,2-difluorocycloheptyl, 2,3-difluorocycloheptyl, 2,4-difluorocycloheptyl, 2,5-difluorocycloheptyl, 2,6-difluorocycloheptyl, 2,7-difluorocycloheptyl, 3,3-difluorocycloheptyl, 3,4-difluorocycloheptyl, 3,5-difluorocycloheptyl, 3,6-difluorocycloheptyl, 4,4-difluorocycloheptyl, 4,5-difluorocycloheptyl, and the like.

[0061] C.sub.2-C.sub.4-Alkenyl is a singly unsaturated hydrocarbon radical having 2, 3 or 4 C-atoms and one C--C double bond, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, buten-1-yl, buten-2-yl, buten-3-yl, methallyl (2-methylprop-2-en-1-yl) and the like.

[0062] C.sub.2-C.sub.4-Haloalkenyl is a singly unsaturated hydrocarbon radical having 2, 3 or 4 C-atoms, wherein at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by halogen atoms, preferably by fluorine atoms such as in 1-fluorovinyl, 2-fluorovinyl, 2,2-fluorovinyl, 3,3,3-fluoropropenyl, 1,1-difluoro-2-propenyl, 1-fluoro-2-propenyl and the like.

[0063] Examples for 5- or 6-membered N- or C-bound heteroaromatic radicals comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members are pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, [1,2,3]-1H-triazol-1-yl, [1,2,3]-1H-triazol-4-yl, [1,2,3]-1H-triazol-5-yl, [1,2,3]-2H-triazol-2-yl, [1,2,3]-2H-triazol-4-yl, [1,2,3]-2H-triazol-5-yl, [1,2,4]-1H-triazol-1-yl, [1,2,4]-1H-triazol-3-yl, [1,2,4]-1H-triazol-5-yl, [1,2,4]-4H-triazol-3-yl, [1,2,4]-4H-triazol-4-yl, oxadiazolyl, thiadiazolyl, [1,2,3,4]-1H-tetrazol-1-yl, [1,2,3,4]-1H-tetrazol-5-yl, [1,2,3,4]-2H-tetrazol-2-yl, [1,2,3,4]-2H-tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl and triazin-2-yl.

[0064] Examples for 5- or 6-membered N- or C-bound heteroaromatic radicals comprising 1, 2 or 3 heteroatoms independently selected from O, S and N as ring members are furan-2-yl, furan-3-yl, thien-2-yl, thien-3-yl, pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, [1,2,3]-1H-triazol-1-yl, [1,2,3]-1H-triazol-4-yl, [1,2,3]-1H-triazol-5-yl, [1,2,3]-2H-triazol-2-yl, [1,2,3]-2H-triazol-4-yl, [1,2,3]-2H-triazol-5-yl, [1,2,4]-1H-triazol-1-yl, [1,2,4]-1H-triazol-3-yl, [1,2,4]-1H-triazol-5-yl, [1,2,4]-4H-triazol-3-yl, [1,2,4]-4H-triazol-4-yl, oxadiazolyl, thiadiazolyl, [1,2,3,4]-1H-tetrazol-1-yl, [1,2,3,4]-1H-tetrazol-5-yl, [1,2,3,4]-2H-tetrazol-2-yl, [1,2,3,4]-2H-tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl and triazin-2-yl.

[0065] Examples for N-bound 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic rings, which may contain 1 further heteroatom or heteroatom-containing group selected from the group consisting of O, S, SO, SO.sub.2 and N as a ring member (thus as rings formed by R.sup.a and R.sup.b together with the nitrogen atom to which they are bound), are aziridin-1-yl, azetidin-1-yl, pyrrolidin-1-yl, pyrazolidin-1-yl, imidazolidin-1-yl, oxazolidin-3-yl, isoxazolidin-2-yl, thiazolidin-3-yl, isothiazolidin-1-yl, [1,2,3]-triazolidin-1-yl, [1,2,3]-triazolidin-2-yl, [1,2,4]-triazolidin-1-yl, [1,2,4]-triazolidin-4-yl, piperidin-1-yl, piperazin-1-yl, morpholin-4-yl, thiomorpholin-1-yl, 1-oxohiomorpholin-1-yl, 1,1-dioxothiomorpholin-1-yl, azepan-1-yl, azirin-1-yl, azetin-1-yl, pyrrolin-1-yl, pyrazolin-1-yl, imidazolin-1-yl, oxazolin-3-yl, isoxazolin-2-yl, thiazolin-3-yl, isothiazolin-1-yl, 1,2-dihydropyridin-1-yl, 1,2,3,4-tetrahydropyridin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl, 1,2-dihydropyridazin, 1,6-dihydropyridazin, 1,2,3,4-tetrahydropyridazin-1-yl, 1,2,5,6-tetrahydropyridazin-1-yl, 1,2-dihydropyrimidin, 1,6-dihydropyrimidin, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,5,6-tetrahydropyrimidin-1-yl, 1,2-dihydropyrazin-1-yl, 1,2,3,4-tetrahydropyrazin-1-yl, 1,2,5,6-tetrahydropyrazin-1-yl, pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, [1,2,3]-1H-triazol-1-yl, [1,2,3]-2H-triazol-2-yl, [1,2,4]-1H-triazol-1-yl and [1,2,4]-4H-triazol-4-yl.

[0066] Examples for saturated, partially unsaturated or aromatic 3-, 4-, 5-, 6- or 7-membered heterocyclic radicals comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein two geminally bound substituents may together form a group .dbd.O are the above-listed examples for 5- or 6-membered N- or C-bound heteroaromatic radicals and further 2-oxiranyl, 2-thiiranyl, 1- or 2-aziridinyl, 1-, 2- or 3-azetidinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 3-tetrahydrofuran-2-onyl, 4-tetrahydrofuran-2-onyl, 5-tetrahydrofuran-2-onyl, 2-tetrahydrofuran-3-onyl, 4-tetrahydrofuran-3-onyl, 5-tetrahydrofuran-3-onyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 3-tetrahydrothien-2-onyl, 4-tetrahydrothien-2-onyl, 5-tetrahydrothien-2-onyl, 2-tetrahydrothien-3-onyl, 4-tetrahydrothien-3-onyl, 5-tetrahydrothien-3-onyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 1-pyrrolidin-2-onyl, 3-pyrrolidin-2-onyl, 4-pyrrolidin-2-onyl, 5-pyrrolidin-2-onyl, 1-pyrrolidin-3-onyl, 2-pyrrolidin-3-onyl, 4-pyrrolidin-3-onyl, 5-pyrrolidin-3-onyl, 1-pyrrolidin-2,5-dionyl, 3-pyrrolidin-2,5-dionyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,2,4-triazolidin-3-yl, 1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl, 1,3,4-triazolidin-2-yl, 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl, 2,4-dihydrothien-3-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2-isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazolin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazolin-4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4-isoxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-isothiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3-dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-1-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1,3-dioxan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl, 1,3,5-hexahydrotriazin-2-yl and 1,2,4-hexahydrotriazin-3-yl. For further examples see also the non-aromatic rings A listed below.

[0067] The remarks made above and in the following with respect to preferred aspects of the invention, e.g. to preferred meanings of the variables X.sup.1, X.sup.2, X.sup.3, X.sup.4, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.a, R.sup.b, R.sup.c of compounds IA and IB, to preferred compounds IA and IB and to preferred embodiments of the method or the use according to the invention, apply in each case on their own or in particular to combinations thereof.

[0068] Preferably, each R.sup.1 is independently selected from hydrogen, halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy and COOH. More preferably, each R.sup.1 is independently selected from hydrogen, halogen, COOH and cyano. Preferably, at most one of R.sup.1 is different from hydrogen. In particular, all radicals R.sup.1 are hydrogen or one radical R.sup.1 is different from hydrogen and is preferably halogen, COOH or cyano and the remaining radicals R.sup.1 are hydrogen. Specifically, one R.sup.1 is cyano and the others are hydrogen.

[0069] Preferably, R.sup.2 is hydrogen.

[0070] In an alternatively preferred embodiment, R.sup.2 is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.2-C.sub.4-alkenyl or fluorine.

[0071] Specifically, R.sup.2 is hydrogen, C.sub.1-C.sub.4-haloalkyl, especially C.sub.1-C.sub.4-fluoroalkyl, or allyl and very specifically hydrogen.

[0072] In one preferred embodiment of the invention, R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1, 2 or 3 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O, S, SO, SO.sub.2, NR.sup.c and NO, and where 1, 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8;

with the proviso that in case R.sup.3 and R.sup.4 form together a bridging group --(CH.sub.2).sub.m--, the CH.sub.2 unit bound in the position of R.sup.3 is not replaced by an NR.sup.c group (in other words, the fused pyridyl moiety is not

##STR00003##

wherein the bow stands for --(CH.sub.2).sub.m-1--, wherein 1 or 2 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O, S, SO, SO.sub.2, NR.sup.c and NO, and where 1, 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8; and # is the attachment point to the remainder of the molecule); and with the proviso that R.sup.3, when not being part of the bridging group, is not NR.sup.aR.sup.b (in other words: where the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are independently selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, and where R.sup.4, R.sup.5 and R.sup.6 may independently also be selected from NR.sup.aR.sup.b).

[0073] In an alternatively preferred embodiment, R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1 or 2 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O and NR.sup.c, and where 1 or 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8, where R.sup.c and R.sup.8 have one of the above-given general or, in particular, one of the below-given preferred meanings. Preferably, the above two provisos (i.e. in case R.sup.3 and R.sup.4 form together a bridging group --(CH.sub.2).sub.m--, the CH.sub.2 unit bound in the position of R.sup.3 is not replaced by an NR.sup.c group; and R.sup.3, when not being part of the bridging group, is not NR.sup.aR.sup.b) apply here, too.

[0074] Preferably, m is 3 or 4.

[0075] More preferably, the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2O--, --CH.sub.2OCH.sub.2--, --NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.c--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2O--, --NR.sup.cCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2NR.sup.c--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8, where R.sup.c and R.sup.8 have one of the above-given general or, in particular, one of the below-given preferred meanings. Preferably, the above two provisos (i.e. in case R.sup.3 and R.sup.4 form together a bridging group --(CH.sub.2).sub.m--, the CH.sub.2 unit bound in the position of R.sup.3 is not replaced by an NR.sup.c group; and R.sup.3, when not being part of the bridging group, is not NR.sup.aR.sup.b) apply here, too. Thus, even more preferably, the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2O--, --CH.sub.2OCH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2O--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8, where R.sup.c and R.sup.8 have one of the above-given general or, in particular, one of the below-given preferred meanings.

[0076] In particular, the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.c--, --CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, and more particularly from --CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8, where R.sup.c and R.sup.8 have one of the above-given general or, in particular, one of the below-given preferred meanings.

[0077] Specifically, the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8, where R.sup.c and R.sup.8 have one of the above-given general or, in particular, one of the below-given preferred meanings.

[0078] Preferably, the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are selected from hydrogen, halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, more preferably from hydrogen, halogen, C.sub.1-C.sub.2-alkyl and C.sub.1-C.sub.2-haloalkyl, and are in particular hydrogen.

[0079] Preferably, R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5 (and not R.sup.5 and R.sup.6) form together a bridging group as defined above. More preferably, R.sup.3 and R.sup.4 (and not R.sup.4 and R.sup.5 or R.sup.5 and R.sup.6) form together a bridging group as defined above.

[0080] Preferably, each R.sup.7 is independently selected from halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy and C.sub.1-C.sub.6-haloalkoxy. And more preferably from CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy.

[0081] Preferably, each R.sup.8 is independently selected from the group consisting of halogen, OH, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl, more preferably from halogen, OH, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl and C.sub.1-C.sub.4-haloalkoxycarbonyl, where preferably R.sup.a and R.sup.b are independently selected from hydrogen and C.sub.1-C.sub.4-alkyl, and specifically from OH, halogen, especially fluorine, C.sub.1-C.sub.4-alkoxy, especially methoxy, C.sub.1-C.sub.4-haloalkoxy, especially trifluoromethoxy, and NR.sup.aR.sup.b, where preferably R.sup.a and R.sup.b are independently selected from hydrogen and C.sub.1-C.sub.4-alkyl. Very specifically, each R.sup.8 is independently selected from the group consisting of OH, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy.

[0082] R.sup.a and R.sup.b are, independently of each other, preferably selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl or form together with the nitrogen atom to which they are bound an N-bound 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom-containing group selected from N, O, S, SO and SO.sub.2 as a ring member, where the N-heterocyclic ring may carry 1 or 2 radicals selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, and are more preferably selected from hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl or form together with the nitrogen atom to which they are bound an N-bound 5- or 6-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom-containing group selected from N and O as a ring member, where the N-heterocyclic ring may carry 1 or 2 radicals selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy.

[0083] Preferably, each R.sup.c is independently selected from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl, more preferably from hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl, even more preferably from hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.4-haloalkoxycarbonyl, and in particular from hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl and C.sub.1-C.sub.6-alkoxycarbonyl. Specifically, each R.sup.c is independently selected from hydrogen and C.sub.1-C.sub.6-alkoxycarbonyl.

[0084] Preferably, all of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are CR.sup.1 or one of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 is N and the others are CR.sup.1. More preferably, all of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are CR.sup.1. Even more preferably, X.sup.1, X.sup.2 and X.sup.4 are CH and X.sup.3 is CR.sup.1, wherein R.sup.1 has one of the above-given general or preferred definitions and is preferably H, COOH or CN. Specifically, X.sup.1, X.sup.2 and X.sup.4 are CH and X.sup.3 is CR.sup.1, wherein R.sup.1 is different from H and is preferably COOH or CN. In particular, X.sup.1, X.sup.2 and X.sup.4 are CH and X.sup.3 is CR.sup.1, wherein R.sup.1 is CN.

[0085] A particularly preferred embodiment of the invention relates to compounds of the formulae IA-1 and IB-1

##STR00004##

wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 have one of the general meanings or, in particular, one of the preferred meanings given above.

[0086] Compounds IA-1 and compounds IB-1 wherein R.sup.2 is H are tautomers and thus the formulae can be used interchangeably.

[0087] Suitable compounds IA and IB are those of formulae I.1 to I.144, the stereoisomers, prodrugs, tautomers and/or physiologically tolerated acid addition salts thereof, wherein R.sup.1, R.sup.2 and R.sup.c have the above-defined general or preferred meanings and R.sup.81 is hydrogen or has one of the above-defined general or preferred meanings given for R.sup.8. Particularly preferred meanings of R.sup.1, R.sup.2, R.sup.81 and R.sup.c specifically in compounds of formulae I.1 to I.144 are as defined below.

##STR00005## ##STR00006## ##STR00007## ##STR00008## ##STR00009## ##STR00010## ##STR00011## ##STR00012## ##STR00013## ##STR00014## ##STR00015## ##STR00016## ##STR00017## ##STR00018## ##STR00019## ##STR00020## ##STR00021## ##STR00022## ##STR00023## ##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028## ##STR00029## ##STR00030## ##STR00031## ##STR00032## ##STR00033## ##STR00034##

[0088] Examples of preferred compounds which are represented by the formulae I.1 to I.144 are the individual compounds compiled in the tables 1 to 6192 below, where the variables R.sup.1 and R.sup.2 have the meanings given in one row of Table A. Moreover, the meanings mentioned for the individual variables in the tables are per se, independently of the combination in which they are mentioned, a particularly preferred embodiment of the substituents in question. Rings A-1 to A-111 mentioned in the tables are defined below.

[0089] Table 1

[0090] Compounds of the formula I.1 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0091] Table 2

[0092] Compounds of the formula I.2 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0093] Table 3

[0094] Compounds of the formula I.3 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0095] Table 4

[0096] Compounds of the formula I.4 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0097] Table 5

[0098] Compounds of the formula I.5 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0099] Table 6

[0100] Compounds of the formula I.6 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0101] Table 7

[0102] Compounds of the formula I.7 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0103] Table 8

[0104] Compounds of the formula I.8 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0105] Table 9

[0106] Compounds of the formula I.9 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0107] Table 10

[0108] Compounds of the formula I.10 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0109] Table 11

[0110] Compounds of the formula I.11 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0111] Table 12

[0112] Compounds of the formula I.12 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0113] Table 13

[0114] Compounds of the formula I.13 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0115] Table 14

[0116] Compounds of the formula I.14 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0117] Table 15

[0118] Compounds of the formula I.15 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0119] Table 16

[0120] Compounds of the formula I.16 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0121] Table 17

[0122] Compounds of the formula I.17 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0123] Table 18

[0124] Compounds of the formula I.18 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0125] Table 19

[0126] Compounds of the formula I.19 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0127] Table 20

[0128] Compounds of the formula I.20 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0129] Table 21

[0130] Compounds of the formula I.21 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0131] Table 22

[0132] Compounds of the formula I.22 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0133] Table 23

[0134] Compounds of the formula I.23 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0135] Table 24

[0136] Compounds of the formula I.24 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0137] Table 25

[0138] Compounds of the formula I.25 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0139] Table 26

[0140] Compounds of the formula I.26 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0141] Table 27

[0142] Compounds of the formula I.27 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0143] Table 28

[0144] Compounds of the formula I.28 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0145] Table 29

[0146] Compounds of the formula I.29 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0147] Table 30

[0148] Compounds of the formula I.30 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0149] Table 31

[0150] Compounds of the formula I.31 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0151] Table 32

[0152] Compounds of the formula I.32 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0153] Table 33

[0154] Compounds of the formula I.33 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0155] Table 34

[0156] Compounds of the formula I.34 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0157] Table 35

[0158] Compounds of the formula I.35 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0159] Table 36

[0160] Compounds of the formula I.36 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0161] Table 37

[0162] Compounds of the formula I.37 in which R.sup.81 is hydrogen and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0163] Table 38

[0164] Compounds of the formula I.37 in which R.sup.81 is methyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0165] Table 39

[0166] Compounds of the formula I.37 in which R.sup.81 is ethyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0167] Table 40

[0168] Compounds of the formula I.37 in which R.sup.81 is propyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0169] Table 41

[0170] Compounds of the formula I.37 in which R.sup.81 is isopropyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0171] Table 42

[0172] Compounds of the formula I.37 in which R.sup.81 is CH.sub.2F and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0173] Table 43

[0174] Compounds of the formula I.37 in which R.sup.81 is CHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0175] Table 44

[0176] Compounds of the formula I.37 in which R.sup.81 is CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0177] Table 45

[0178] Compounds of the formula I.37 in which R.sup.81 is CH.sub.2CHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0179] Table 46

[0180] Compounds of the formula I.37 in which R.sup.81 is CH.sub.2CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0181] Table 47

[0182] Compounds of the formula I.37 in which R.sup.81 is F and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0183] Table 48

[0184] Compounds of the formula I.37 in which R.sup.81 is Cl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0185] Table 49

[0186] Compounds of the formula I.37 in which R.sup.81 is Br and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0187] Table 50

[0188] Compounds of the formula I.37 in which R.sup.81 is OH and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0189] Table 51

[0190] Compounds of the formula I.37 in which R.sup.81 is methoxy and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0191] Table 52

[0192] Compounds of the formula I.37 in which R.sup.81 is ethoxy and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0193] Table 53

[0194] Compounds of the formula I.37 in which R.sup.81 is propoxy and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0195] Table 54

[0196] Compounds of the formula I.37 in which R.sup.81 is isopropoxy and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0197] Table 55

[0198] Compounds of the formula I.37 in which R.sup.81 is OCHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0199] Table 56

[0200] Compounds of the formula I.37 in which R.sup.81 is OCF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0201] Table 57

[0202] Compounds of the formula I.37 in which R.sup.81 is OCH.sub.2CHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0203] Table 58

[0204] Compounds of the formula I.37 in which R.sup.81 is OCH.sub.2CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0205] Table 59

[0206] Compounds of the formula I.37 in which R.sup.81 is NH.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0207] Table 60

[0208] Compounds of the formula I.37 in which R.sup.81 is methylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0209] Table 61

[0210] Compounds of the formula I.37 in which R.sup.81 is dimethylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0211] Table 62

[0212] Compounds of the formula I.37 in which R.sup.81 is ethylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0213] Table 63

[0214] Compounds of the formula I.37 in which R.sup.81 is diethylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0215] Table 64

[0216] Compounds of the formula I.37 in which R.sup.81 is propylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0217] Table 65

[0218] Compounds of the formula I.37 in which R.sup.81 is dipropylamino and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0219] Table 66

[0220] Compounds of the formula I.37 in which R.sup.81 is NHC(O)CH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0221] Table 67

[0222] Compounds of the formula I.37 in which R.sup.81 is NHC(O)CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0223] Table 68

[0224] Compounds of the formula I.37 in which R.sup.81 is NHC(O)OCH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0225] Table 69

[0226] Compounds of the formula I.37 in which R.sup.81 is NHC(O)OCF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0227] Table 70

[0228] Compounds of the formula I.37 in which R.sup.81 is NHC(O)OC(CH.sub.3).sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0229] Table 71

[0230] Compounds of the formula I.37 in which R.sup.81 is cyclopropyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0231] Table 72

[0232] Compounds of the formula I.37 in which R.sup.81 is cyclobutyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0233] Table 73

[0234] Compounds of the formula I.37 in which R.sup.81 is cyclopentyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0235] Table 74

[0236] Compounds of the formula I.37 in which R.sup.81 is cyclohexyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0237] Table 75

[0238] Compounds of the formula I.37 in which R.sup.81 is cycloheptyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0239] Table 76

[0240] Compounds of the formula I.37 in which R.sup.81 is A-1 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0241] Table 77

[0242] Compounds of the formula I.37 in which R.sup.81 is A-2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0243] Table 78

[0244] Compounds of the formula I.37 in which R.sup.81 is A-3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0245] Table 79

[0246] Compounds of the formula I.37 in which R.sup.81 is A-4 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0247] Table 80

[0248] Compounds of the formula I.37 in which R.sup.81 is A-5 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0249] Table 81

[0250] Compounds of the formula I.37 in which R.sup.81 is A-6 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0251] Table 82

[0252] Compounds of the formula I.37 in which R.sup.81 is A-7 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0253] Table 83

[0254] Compounds of the formula I.37 in which R.sup.81 is A-8 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0255] Table 84

[0256] Compounds of the formula I.37 in which R.sup.81 is A-9 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0257] Table 85

[0258] Compounds of the formula I.37 in which R.sup.81 is A-10 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0259] Table 86

[0260] Compounds of the formula I.37 in which R.sup.81 is A-11 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0261] Table 87

[0262] Compounds of the formula I.37 in which R.sup.81 is A-12 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0263] Table 88

[0264] Compounds of the formula I.37 in which R.sup.81 is A-13 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0265] Table 89

[0266] Compounds of the formula I.37 in which R.sup.81 is A-14 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0267] Table 90

[0268] Compounds of the formula I.37 in which R.sup.81 is A-15 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0269] Table 91

[0270] Compounds of the formula I.37 in which R.sup.81 is A-16 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0271] Table 92

[0272] Compounds of the formula I.37 in which R.sup.81 is A-17 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0273] Table 93

[0274] Compounds of the formula I.37 in which R.sup.81 is A-18 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0275] Table 94

[0276] Compounds of the formula I.37 in which R.sup.81 is A-19 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0277] Table 95

[0278] Compounds of the formula I.37 in which R.sup.81 is A-20 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0279] Table 96

[0280] Compounds of the formula I.37 in which R.sup.81 is A-21 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0281] Table 97

[0282] Compounds of the formula I.37 in which R.sup.81 is A-22 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0283] Table 98

[0284] Compounds of the formula I.37 in which R.sup.81 is A-23 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0285] Table 99

[0286] Compounds of the formula I.37 in which R.sup.81 is A-24 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0287] Table 100

[0288] Compounds of the formula I.37 in which R.sup.81 is A-25 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0289] Table 101

[0290] Compounds of the formula I.37 in which R.sup.81 is A-26 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0291] Table 102

[0292] Compounds of the formula I.37 in which R.sup.81 is A-27 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0293] Table 103

[0294] Compounds of the formula I.37 in which R.sup.81 is A-28 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0295] Table 104

[0296] Compounds of the formula I.37 in which R.sup.81 is A-29 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0297] Table 105

[0298] Compounds of the formula I.37 in which R.sup.81 is A-30 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0299] Table 106

[0300] Compounds of the formula I.37 in which R.sup.81 is A-31 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0301] Table 107

[0302] Compounds of the formula I.37 in which R.sup.81 is A-32 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0303] Table 108

[0304] Compounds of the formula I.37 in which R.sup.81 is A-33 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0305] Table 109

[0306] Compounds of the formula I.37 in which R.sup.81 is A-34 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0307] Table 110

[0308] Compounds of the formula I.37 in which R.sup.81 is A-35 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0309] Table 111

[0310] Compounds of the formula I.37 in which R.sup.81 is A-36 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0311] Table 112

[0312] Compounds of the formula I.37 in which R.sup.81 is A-37 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0313] Table 113

[0314] Compounds of the formula I.37 in which R.sup.81 is A-38 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0315] Table 114

[0316] Compounds of the formula I.37 in which R.sup.81 is A-39 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0317] Table 115

[0318] Compounds of the formula I.37 in which R.sup.81 is A-40 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0319] Table 116

[0320] Compounds of the formula I.37 in which R.sup.81 is A-41 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0321] Table 117

[0322] Compounds of the formula I.37 in which R.sup.81 is A-42 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0323] Table 118

[0324] Compounds of the formula I.37 in which R.sup.81 is A-43 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0325] Table 119

[0326] Compounds of the formula I.37 in which R.sup.81 is A-44 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0327] Table 120

[0328] Compounds of the formula I.37 in which R.sup.81 is A-45 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0329] Table 121

[0330] Compounds of the formula I.37 in which R.sup.81 is A-46 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0331] Table 122

[0332] Compounds of the formula I.37 in which R.sup.81 is A-47 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0333] Table 123

[0334] Compounds of the formula I.37 in which R.sup.81 is A-48 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0335] Table 124

[0336] Compounds of the formula I.37 in which R.sup.81 is A-49 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0337] Table 125

[0338] Compounds of the formula I.37 in which R.sup.81 is A-50 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0339] Table 126

[0340] Compounds of the formula I.37 in which R.sup.81 is A-51 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0341] Table 127

[0342] Compounds of the formula I.37 in which R.sup.81 is A-52 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0343] Table 128

[0344] Compounds of the formula I.37 in which R.sup.81 is A-53 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0345] Table 129

[0346] Compounds of the formula I.37 in which R.sup.81 is A-54 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0347] Table 130

[0348] Compounds of the formula I.37 in which R.sup.81 is A-55 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0349] Table 131

[0350] Compounds of the formula I.37 in which R.sup.81 is A-56 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0351] Table 132

[0352] Compounds of the formula I.37 in which R.sup.81 is A-57 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0353] Table 133

[0354] Compounds of the formula I.37 in which R.sup.81 is A-58 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0355] Table 134

[0356] Compounds of the formula I.37 in which R.sup.81 is A-59 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0357] Table 135

[0358] Compounds of the formula I.37 in which R.sup.81 is A-60 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0359] Table 136

[0360] Compounds of the formula I.37 in which R.sup.81 is A-61 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0361] Table 137

[0362] Compounds of the formula I.37 in which R.sup.81 is A-62 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0363] Table 138

[0364] Compounds of the formula I.37 in which R.sup.81 is A-63 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0365] Table 139

[0366] Compounds of the formula I.37 in which R.sup.81 is A-64 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0367] Table 140

[0368] Compounds of the formula I.37 in which R.sup.81 is A-65 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0369] Table 141

[0370] Compounds of the formula I.37 in which R.sup.81 is A-66 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0371] Table 142

[0372] Compounds of the formula I.37 in which R.sup.81 is A-67 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0373] Table 143

[0374] Compounds of the formula I.37 in which R.sup.81 is A-68 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0375] Table 144

[0376] Compounds of the formula I.37 in which R.sup.81 is A-69 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0377] Table 145

[0378] Compounds of the formula I.37 in which R.sup.81 is A-70 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0379] Table 146

[0380] Compounds of the formula I.37 in which R.sup.81 is A-71 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0381] Table 147

[0382] Compounds of the formula I.37 in which R.sup.81 is A-72 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0383] Table 148

[0384] Compounds of the formula I.37 in which R.sup.81 is A-73 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0385] Table 149

[0386] Compounds of the formula I.37 in which R.sup.81 is A-74 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0387] Table 150

[0388] Compounds of the formula I.37 in which R.sup.81 is A-75 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0389] Table 151

[0390] Compounds of the formula I.37 in which R.sup.81 is A-76 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0391] Table 152

[0392] Compounds of the formula I.37 in which R.sup.81 is A-77 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0393] Table 153

[0394] Compounds of the formula I.37 in which R.sup.81 is A-78 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0395] Table 154

[0396] Compounds of the formula I.37 in which R.sup.81 is A-79 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0397] Table 155

[0398] Compounds of the formula I.37 in which R.sup.81 is A-80 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0399] Table 156

[0400] Compounds of the formula I.37 in which R.sup.81 is A-81 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0401] Table 157

[0402] Compounds of the formula I.37 in which R.sup.81 is A-82 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0403] Table 158

[0404] Compounds of the formula I.37 in which R.sup.81 is A-83 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0405] Table 159

[0406] Compounds of the formula I.37 in which R.sup.81 is A-84 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0407] Table 160

[0408] Compounds of the formula I.37 in which R.sup.81 is A-85 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0409] Table 161

[0410] Compounds of the formula I.37 in which R.sup.81 is A-86 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0411] Table 162

[0412] Compounds of the formula I.37 in which R.sup.81 is A-87 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0413] Table 163

[0414] Compounds of the formula I.37 in which R.sup.81 is A-88 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0415] Table 164

[0416] Compounds of the formula I.37 in which R.sup.81 is A-89 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0417] Table 165

[0418] Compounds of the formula I.37 in which R.sup.81 is A-90 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0419] Table 166

[0420] Compounds of the formula I.37 in which R.sup.81 is A-91 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0421] Table 167

[0422] Compounds of the formula I.37 in which R.sup.81 is A-92 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0423] Table 168

[0424] Compounds of the formula I.37 in which R.sup.81 is A-93 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0425] Table 169

[0426] Compounds of the formula I.37 in which R.sup.81 is A-94 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0427] Table 170

[0428] Compounds of the formula I.37 in which R.sup.81 is A-95 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0429] Table 171

[0430] Compounds of the formula I.37 in which R.sup.81 is A-96 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0431] Table 172

[0432] Compounds of the formula I.37 in which R.sup.81 is A-97 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0433] Table 173

[0434] Compounds of the formula I.37 in which R.sup.81 is A-98 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0435] Table 174

[0436] Compounds of the formula I.37 in which R.sup.81 is A-99 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0437] Table 175

[0438] Compounds of the formula I.37 in which R.sup.81 is A-100 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0439] Table 176

[0440] Compounds of the formula I.37 in which R.sup.81 is A-101 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0441] Table 177

[0442] Compounds of the formula I.37 in which R.sup.81 is A-102 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0443] Table 178

[0444] Compounds of the formula I.37 in which R.sup.81 is A-103 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0445] Table 179

[0446] Compounds of the formula I.37 in which R.sup.81 is A-104 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0447] Table 180

[0448] Compounds of the formula I.37 in which R.sup.81 is A-105 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0449] Table 181

[0450] Compounds of the formula I.37 in which R.sup.81 is A-106 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0451] Table 182

[0452] Compounds of the formula I.37 in which R.sup.81 is A-107 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0453] Table 183

[0454] Compounds of the formula I.37 in which R.sup.81 is A-108 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0455] Table 184

[0456] Compounds of the formula I.37 in which R.sup.81 is A-109 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0457] Table 185

[0458] Compounds of the formula I.37 in which R.sup.81 is A-110 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0459] Table 186

[0460] Compounds of the formula I.37 in which R.sup.81 is A-111 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0461] Tables 37 to 336

[0462] Compounds of the formula I.38 in which R.sup.81 is as defined in tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0463] Tables 337 to 486

[0464] Compounds of the formula I.39 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0465] Tables 487 to 636

[0466] Compounds of the formula I.40 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0467] Tables 637 to 786

[0468] Compounds of the formula I.41 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0469] Tables 787 to 936

[0470] Compounds of the formula I.42 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0471] Tables 937 to 1086

[0472] Compounds of the formula I.43 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0473] Tables 1087 to 1236

[0474] Compounds of the formula I.44 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0475] Tables 1237 to 1386

[0476] Compounds of the formula I.45 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0477] Tables 1387 to 1536

[0478] Compounds of the formula I.46 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0479] Tables 1537 to 1686

[0480] Compounds of the formula I.47 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0481] Tables 1687 to 1836

[0482] Compounds of the formula I.48 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0483] Tables 1837 to 1986

[0484] Compounds of the formula I.49 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0485] Tables 1987 to 2136

[0486] Compounds of the formula I.50 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0487] Tables 2137 to 2286

[0488] Compounds of the formula I.51 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0489] Tables 2287 to 2436

[0490] Compounds of the formula I.52 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0491] Tables 2437 to 2586

[0492] Compounds of the formula I.53 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0493] Tables 2587 to 2736

[0494] Compounds of the formula I.54 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0495] Tables 2737 to 2886

[0496] Compounds of the formula I.55 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0497] Tables 2887 to 3036

[0498] Compounds of the formula I.56 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0499] Tables 3037 to 3186

[0500] Compounds of the formula I.57 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0501] Tables 3187 to 3336

[0502] Compounds of the formula I.58 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0503] Tables 3337 to 3486

[0504] Compounds of the formula I.59 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0505] Tables 3487 to 3636

[0506] Compounds of the formula I.60 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0507] Tables 3637 to 3786

[0508] Compounds of the formula I.61 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0509] Tables 3787 to 3936

[0510] Compounds of the formula I.62 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0511] Tables 3937 to 4086

[0512] Compounds of the formula I.63 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0513] Tables 4087 to 4236

[0514] Compounds of the formula I.64 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0515] Tables 4237 to 4386

[0516] Compounds of the formula I.65 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0517] Tables 4387 to 4536

[0518] Compounds of the formula I.66 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0519] Tables 4537 to 4686

[0520] Compounds of the formula I.67 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0521] Tables 4687 to 4836

[0522] Compounds of the formula I.68 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0523] Tables 4837 to 4986

[0524] Compounds of the formula I.69 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0525] Tables 4987 to 5136

[0526] Compounds of the formula I.70 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0527] Tables 5137 to 5286

[0528] Compounds of the formula I.71 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0529] Tables 5287 to 5436

[0530] Compounds of the formula I.72 in which R.sup.81 is as defined in Tables 37 to 186 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0531] Table 5437

[0532] Compounds of the formula I.73 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0533] Table 5438

[0534] Compounds of the formula I.74 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0535] Table 5439

[0536] Compounds of the formula I.75 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0537] Table 5440

[0538] Compounds of the formula I.76 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0539] Table 5441

[0540] Compounds of the formula I.77 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0541] Table 5442

[0542] Compounds of the formula I.78 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0543] Table 5443

[0544] Compounds of the formula I.79 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0545] Table 5444

[0546] Compounds of the formula I.80 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0547] Table 5445

[0548] Compounds of the formula I.81 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0549] Table 5446

[0550] Compounds of the formula I.82 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0551] Table 5447

[0552] Compounds of the formula I.83 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0553] Table 5448

[0554] Compounds of the formula I.84 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0555] Table 5449

[0556] Compounds of the formula I.85 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0557] Table 5450

[0558] Compounds of the formula I.86 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0559] Table 5451

[0560] Compounds of the formula I.87 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0561] Table 5452

[0562] Compounds of the formula I.88 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0563] Table 5453

[0564] Compounds of the formula I.89 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0565] Table 5454

[0566] Compounds of the formula I.90 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0567] Table 5455

[0568] Compounds of the formula I.91 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0569] Table 5456

[0570] Compounds of the formula I.92 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0571] Table 5457

[0572] Compounds of the formula I.93 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0573] Table 5458

[0574] Compounds of the formula I.94 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0575] Table 5459

[0576] Compounds of the formula I.95 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0577] Table 5460

[0578] Compounds of the formula I.96 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0579] Table 5461

[0580] Compounds of the formula I.97 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0581] Table 5462

[0582] Compounds of the formula I.98 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0583] Table 5463

[0584] Compounds of the formula I.99 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0585] Table 5464

[0586] Compounds of the formula I.100 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0587] Table 5465

[0588] Compounds of the formula I.101 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0589] Table 5466

[0590] Compounds of the formula I.102 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0591] Table 5467

[0592] Compounds of the formula I.103 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0593] Table 5468

[0594] Compounds of the formula I.104 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0595] Table 5469

[0596] Compounds of the formula I.105 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0597] Table 5470

[0598] Compounds of the formula I.106 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0599] Table 5471

[0600] Compounds of the formula I.107 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0601] Table 5472

[0602] Compounds of the formula I.108 in which the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0603] Table 5473

[0604] Compounds of the formula I.109 in which R.sup.c is hydrogen and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0605] Table 5474

[0606] Compounds of the formula I.109 in which R.sup.c is methyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0607] Table 5475

[0608] Compounds of the formula I.109 in which R.sup.c is ethyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0609] Table 5476

[0610] Compounds of the formula I.109 in which R.sup.c is propyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0611] Table 5477

[0612] Compounds of the formula I.109 in which R.sup.c is isopropyl and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0613] Table 5478

[0614] Compounds of the formula I.109 in which R.sup.c is CH.sub.2OCH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0615] Table 5479

[0616] Compounds of the formula I.109 in which R.sup.c is CH.sub.2CH.sub.2OCH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0617] Table 5480

[0618] Compounds of the formula I.109 in which R.sup.c is CH.sub.2CH.sub.2OCH.sub.2CH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A. Table 5481

[0619] Compounds of the formula I.109 in which R.sup.c is CHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0620] Table 5482

[0621] Compounds of the formula I.109 in which R.sup.c is CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0622] Table 5483

[0623] Compounds of the formula I.109 in which R.sup.c is CH.sub.2CHF.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0624] Table 5484

[0625] Compounds of the formula I.109 in which R.sup.c is CH.sub.2CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0626] Table 5485

[0627] Compounds of the formula I.109 in which R.sup.c is CF.sub.2CF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0628] Table 5486

[0629] Compounds of the formula I.109 in which R.sup.c is C(O)CH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0630] Table 5487

[0631] Compounds of the formula I.109 in which R.sup.c is C(O)OCH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0632] Table 5488

[0633] Compounds of the formula I.109 in which R.sup.c is C(O)OCF.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0634] Table 5489

[0635] Compounds of the formula I.109 in which R.sup.c is C(O)OC(CH.sub.3).sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0636] Table 5490

[0637] Compounds of the formula I.109 in which R.sup.c is C(O)NH.sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0638] Table 5491

[0639] Compounds of the formula I.109 in which R.sup.c is C(O)NHCH.sub.3 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0640] Table 5492

[0641] Compounds of the formula I.109 in which R.sup.c is C(O)N(CH.sub.3).sub.2 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0642] Tables 5493 to 5512

[0643] Compounds of the formula I.110 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0644] Tables 5513 to 5532

[0645] Compounds of the formula I.111 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0646] Tables 5533 to 5552

[0647] Compounds of the formula I.112 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0648] Tables 5553 to 5572

[0649] Compounds of the formula I.113 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0650] Tables 5573 to 5592

[0651] Compounds of the formula I.114 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0652] Tables 5593 to 5612

[0653] Compounds of the formula I.115 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0654] Tables 5613 to 5632

[0655] Compounds of the formula I.116 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0656] Tables 5633 to 5652

[0657] Compounds of the formula I.117 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0658] Tables 5653 to 5672

[0659] Compounds of the formula I.118 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0660] Tables 5673 to 5692

[0661] Compounds of the formula I.119 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0662] Tables 5693 to 5712

[0663] Compounds of the formula I.120 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0664] Tables 5713 to 5732

[0665] Compounds of the formula I.121 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0666] Tables 5733 to 5752

[0667] Compounds of the formula I.122 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0668] Tables 5753 to 5772

[0669] Compounds of the formula I.123 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0670] Tables 5773 to 5792

[0671] Compounds of the formula I.124 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0672] Tables 5793 to 5812

[0673] Compounds of the formula I.125 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0674] Tables 5813 to 5832

[0675] Compounds of the formula I.126 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0676] Tables 5833 to 5852

[0677] Compounds of the formula I.127 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0678] Tables 5853 to 5872

[0679] Compounds of the formula I.128 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0680] Tables 5873 to 5892

[0681] Compounds of the formula I.129 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0682] Tables 5893 to 5912

[0683] Compounds of the formula I.130 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0684] Tables 5913 to 5932

[0685] Compounds of the formula I.131 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0686] Tables 5933 to 5952

[0687] Compounds of the formula I.132 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0688] Tables 5953 to 5972

[0689] Compounds of the formula I.133 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0690] Tables 5973 to 5992

[0691] Compounds of the formula I.134 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0692] Tables 5993 to 6012

[0693] Compounds of the formula I.135 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0694] Tables 6013 to 6032

[0695] Compounds of the formula I.136 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0696] Tables 6033 to 6052

[0697] Compounds of the formula I.137 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0698] Tables 6053 to 6072

[0699] Compounds of the formula I.138 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0700] Tables 6073 to 6092

[0701] Compounds of the formula I.139 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0702] Tables 6093 to 6112

[0703] Compounds of the formula I.140 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0704] Tables 6113 to 6132

[0705] Compounds of the formula I.141 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0706] Tables 6133 to 6152

[0707] Compounds of the formula I.142 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0708] Tables 6153 to 6172

[0709] Compounds of the formula I.143 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0710] Tables 6173 to 6192

[0711] Compounds of the formula I.144 in which R.sup.c is as defined in Tables 5472 to 5492 and the combination of R.sup.1 and R.sup.2 for a compound corresponds in each case to one row of Table A.

[0712] Rings A

[0713] "#" marks the attachment point to the remainder of the molecule

##STR00035## ##STR00036## ##STR00037## ##STR00038## ##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043## ##STR00044## ##STR00045##

[0714] In Table A, the position of R.sup.1 is characterized as follows:

TABLE-US-00001 TABLE A ##STR00046## No. R.sup.2 R.sup.1 A-1 H H A-2 H 4-Cl A-3 H 5-Cl A-4 H 6-Cl A-5 H 7-Cl A-6 H 4-Br A-7 H 5-Br A-8 H 6-Br A-9 H 7-Br A-10 H 4-CN A-11 H 5-CN A-12 H 6-CN A-13 H 7-CN A-14 H 4-OH A-15 H 5-OH A-16 H 6-OH A-17 H 7-OH A-18 H 4-methyl A-19 H 5-methyl A-20 H 6-methyl A-21 H 7-methyl A-22 H 4-ethyl A-23 H 5-ethyl A-24 H 6-ethyl A-25 H 7-ethyl A-26 H 4-propyl A-27 H 5-propyl A-28 H 6-propyl A-29 H 7-propyl A-30 H 4-isopropyl A-31 H 5-isopropyl A-32 H 6-isopropyl A-33 H 7-isopropyl A-34 H 4-hydroxymethyl A-35 H 5-hydroxymethyl A-36 H 6-hydroxymethyl A-37 H 7-hydroxymethyl A-38 H 4-(2-hydroxyethyl) A-39 H 5-(2-hydroxyethyl) A-40 H 6-(2-hydroxyethyl) A-41 H 7-(2-hydroxyethyl) A-42 H 4-(1-hydroxyethyl) A-43 H 5-(1-hydroxyethyl) A-44 H 6-(1-hydroxyethyl) A-45 H 7-(1-hydroxyethyl) A-46 H 4-(3-hydroxypropyl) A-47 H 5-(3-hydroxypropyl) A-48 H 6-(3-hydroxypropyl) A-49 H 7-(3-hydroxypropyl) A-50 H 4-(2-hydroxypropyl) A-51 H 5-(2-hydroxypropyl) A-52 H 6-(2-hydroxypropyl) A-53 H 7-(2-hydroxypropyl) A-54 H 4-(1-hydroxypropyl) A-55 H 5-(1-hydroxypropyl) A-56 H 6-(1-hydroxypropyl) A-57 H 7-(1-hydroxypropyl) A-58 H 4-aminomethyl A-59 H 5-aminomethyl A-60 H 6-aminomethyl A-61 H 7-aminomethyl A-62 H 4-(2-aminoethyl) A-63 H 5-(2-aminoethyl) A-64 H 6-(2-aminoethyl) A-65 H 7-(2-aminoethyl) A-66 H 4-(1-aminoethyl) A-67 H 5-(1-aminoethyl) A-68 H 6-(1-aminoethyl) A-69 H 7-(1-aminoethyl) A-70 H 4-(3-aminopropyl) A-71 H 5-(3-aminopropyl) A-72 H 6-(3-aminopropyl) A-73 H 7-(3-aminopropyl) A-74 H 4-(2-aminopropyl) A-75 H 5-(2-aminopropyl) A-76 H 6-(2-aminopropyl) A-77 H 7-(2-aminopropyl) A-78 H 4-(1-aminopropyl) A-79 H 5-(1-aminopropyl) A-80 H 6-(1-aminopropyl) A-81 H 7-(1-aminopropyl) A-82 H 4-COOH A-83 H 5-COOH A-84 H 6-COOH A-85 H 7-COOH A-86 H 4-COOCH.sub.3 A-87 H 5-COOCH.sub.3 A-88 H 6-COOCH.sub.3 A-89 H 7-COOCH.sub.3 A-90 H 4-COOCH.sub.2CH.sub.3 A-91 H 5-COOCH.sub.2CH.sub.3 A-92 H 6-COOCH.sub.2CH.sub.3 A-93 H 7-COOCH.sub.2CH.sub.3 A-94 H 4-COOCF.sub.3 A-95 H 5-COOCF.sub.3 A-96 H 6-COOCF.sub.3 A-97 H 7-COOCF.sub.3 A-98 H 4-CONH.sub.2 A-99 H 5-CONH.sub.2 A-100 H 6-CONH.sub.2 A-101 H 7-CONH.sub.2 A-102 H 4-CONHCH.sub.3 A-103 H 5-CONHCH.sub.3 A-104 H 6-CONHCH.sub.3 A-105 H 7-CONHCH.sub.3 A-106 H 4-CON(CH.sub.3).sub.2 A-107 H 5-CON(CH.sub.3).sub.2 A-108 H 6-CON(CH.sub.3).sub.2 A-109 H 7-CON(CH.sub.3).sub.2 A-110 H 4-CONHCH.sub.2CH.sub.3 A-111 H 5-CONHCH.sub.2CH.sub.3 A-112 H 6-CONHCH.sub.2CH.sub.3 A-113 H 7-CONHCH.sub.2CH.sub.3 A-114 H 4-CON(CH.sub.2CH.sub.3).sub.2 A-115 H 5-CON(CH.sub.2CH.sub.3).sub.2 A-116 H 6-CON(CH.sub.2CH.sub.3).sub.2 A-117 H 7-CON(CH.sub.2CH.sub.3).sub.2 A-118 H 4-A-1 A-119 H 5-A-1 A-120 H 6-A-1 A-121 H 7-A-1 A-122 H 4-A-2 A-123 H 5-A-2 A-124 H 6-A-2 A-125 H 7-A-2 A-126 H 4-A-3 A-127 H 5-A-3 A-128 H 6-A-3 A-129 H 7-A-3 A-130 H 4-A-4 A-131 H 5-A-4 A-132 H 6-A-4 A-133 H 7-A-4 A-134 H 4-A-5 A-135 H 5-A-5 A-136 H 6-A-5 A-137 H 7-A-5 A-138 H 4-A-6 A-139 H 5-A-6 A-140 H 6-A-6 A-141 H 7-A-6 A-142 H 4-A-7 A-143 H 5-A-7 A-144 H 6-A-7 A-145 H 7-A-7 A-146 H 4-A-8 A-147 H 5-A-8 A-148 H 6-A-8 A-149 H 7-A-8 A-150 H 4-A-9 A-151 H 5-A-9 A-152 H 6-A-9 A-153 H 7-A-9 A-154 H 4-A-10 A-155 H 5-A-10 A-156 H 6-A-10 A-157 H 7-A-10 A-158 H 4-A-11 A-159 H 5-A-11 A-160 H 6-A-11 A-161 H 7-A-11 A-162 H 4-A-12 A-163 H 5-A-12 A-164 H 6-A-12 A-165 H 7-A-12 A-166 H 4-A-13 A-167 H 5-A-13 A-168 H 6-A-13 A-169 H 7-A-13 A-170 H 4-A-14 A-171 H 5-A-14 A-172 H 6-A-14 A-173 H 7-A-14 A-174 H 4-A-15 A-175 H 5-A-15 A-176 H 6-A-15 A-177 H 7-A-15 A-178 H 4-A-16 A-179 H 5-A-16 A-180 H 6-A-16 A-181 H 7-A-16 A-182 H 4-A-17 A-183 H 5-A-17 A-184 H 6-A-17 A-185 H 7-A-17 A-186 H 4-A-18 A-187 H 5-A-18 A-188 H 6-A-18 A-189 H 7-A-18 A-190 H 4-A-19 A-191 H 5-A-19 A-192 H 6-A-19 A-193 H 7-A-19 A-194 H 4-A-20 A-195 H 5-A-20 A-196 H 6-A-20 A-197 H 7-A-20 A-198 H 4-A-21 A-199 H 5-A-21 A-200 H 6-A-21 A-201 H 7-A-21 A-202 H 4-A-22 A-203 H 5-A-22 A-204 H 6-A-22 A-205 H 7-A-22 A-206 H 4-A-23 A-207 H 5-A-23 A-208 H 6-A-23 A-209 H 7-A-23 A-210 H 4-A-24 A-211 H 5-A-24 A-212 H 6-A-24 A-213 H 7-A-24 A-214 H 4-A-25 A-215 H 5-A-25 A-216 H 6-A-25 A-217 H 7-A-25 A-218 H 4-A-26 A-219 H 5-A-26 A-220 H 6-A-26 A-221 H 7-A-26 A-222 H 4-A-27 A-223 H 5-A-27 A-224 H 6-A-27 A-225 H 7-A-27 A-226 H 4-A-28 A-227 H 5-A-28 A-228 H 6-A-28 A-229 H 7-A-28 A-230 H 4-A-29 A-231 H 5-A-29 A-232 H 6-A-29 A-233 H 7-A-29 A-234 H 4-A-30 A-235 H 5-A-30 A-236 H 6-A-30 A-237 H 7-A-30 A-238 H 4-A-31 A-239 H 5-A-31 A-240 H 6-A-31 A-241 H 7-A-31 A-242 H 4-A-32 A-243 H 5-A-32 A-244 H 6-A-32

A-245 H 7-A-32 A-246 H 4-A-33 A-247 H 5-A-33 A-248 H 6-A-33 A-249 H 7-A-33 A-250 H 4-A-34 A-251 H 5-A-34 A-252 H 6-A-34 A-253 H 7-A-34 A-254 H 4-A-35 A-255 H 5-A-35 A-256 H 6-A-35 A-257 H 7-A-35 A-258 H 4-A-36 A-259 H 5-A-36 A-260 H 6-A-36 A-261 H 7-A-36 A-262 H 4-A-37 A-263 H 5-A-37 A-264 H 6-A-37 A-265 H 7-A-37 A-266 H 4-A-38 A-267 H 5-A-38 A-268 H 6-A-38 A-269 H 7-A-38 A-270 H 4-A-39 A-271 H 5-A-39 A-272 H 6-A-39 A-273 H 7-A-39 A-274 H 4-A-40 A-275 H 5-A-40 A-276 H 6-A-40 A-277 H 7-A-40 A-278 H 4-A-41 A-279 H 5-A-41 A-280 H 6-A-41 A-281 H 7-A-41 A-282 H 4-A-42 A-283 H 5-A-42 A-284 H 6-A-42 A-285 H 7-A-42 A-286 H 4-A-43 A-287 H 5-A-43 A-288 H 6-A-43 A-289 H 7-A-43 A-290 H 4-A-44 A-291 H 5-A-44 A-292 H 6-A-44 A-293 H 7-A-44 A-294 H 4-A-45 A-295 H 5-A-45 A-296 H 6-A-45 A-297 H 7-A-45 A-298 H 4-A-46 A-299 H 5-A-46 A-300 H 6-A-46 A-301 H 7-A-46 A-302 H 4-A-47 A-303 H 5-A-47 A-304 H 6-A-47 A-305 H 7-A-47 A-306 H 4-A-48 A-307 H 5-A-48 A-308 H 6-A-48 A-309 H 7-A-48 A-310 H 4-A-49 A-311 H 5-A-49 A-312 H 6-A-49 A-313 H 7-A-49 A-314 H 4-A-50 A-315 H 5-A-50 A-316 H 6-A-50 A-317 H 7-A-50 A-318 H 4-A-51 A-319 H 5-A-51 A-320 H 6-A-51 A-321 H 7-A-51 A-322 H 4-A-52 A-323 H 5-A-52 A-324 H 6-A-52 A-325 H 7-A-52 A-326 H 4-A-53 A-327 H 5-A-53 A-328 H 6-A-53 A-329 H 7-A-53 A-330 H 4-A-54 A-331 H 5-A-54 A-332 H 6-A-54 A-333 H 7-A-54 A-334 H 4-A-55 A-335 H 5-A-55 A-336 H 6-A-55 A-337 H 7-A-55 A-338 H 4-A-56 A-339 H 5-A-56 A-340 H 6-A-56 A-341 H 7-A-56 A-342 H 4-A-57 A-343 H 5-A-57 A-344 H 6-A-57 A-345 H 7-A-57 A-346 H 4-A-58 A-347 H 5-A-58 A-348 H 6-A-58 A-349 H 7-A-58 A-350 H 4-A-59 A-351 H 5-A-59 A-352 H 6-A-59 A-353 H 7-A-59 A-354 H 4-A-60 A-355 H 5-A-60 A-356 H 6-A-60 A-357 H 7-A-60 A-358 H 4-A-61 A-359 H 5-A-61 A-360 H 6-A-61 A-361 H 7-A-61 A-362 H 4-A-62 A-363 H 5-A-62 A-364 H 6-A-62 A-365 H 7-A-62 A-366 H 4-A-63 A-367 H 5-A-63 A-368 H 6-A-63 A-369 H 7-A-63 A-370 H 4-A-64 A-371 H 5-A-64 A-372 H 6-A-64 A-373 H 7-A-64 A-374 H 4-A-65 A-375 H 5-A-65 A-376 H 6-A-65 A-377 H 7-A-65 A-378 H 4-A-66 A-379 H 5-A-66 A-380 H 6-A-66 A-381 H 7-A-66 A-382 H 4-A-67 A-383 H 5-A-67 A-384 H 6-A-67 A-385 H 7-A-67 A-386 H 4-A-68 A-387 H 5-A-68 A-388 H 6-A-68 A-389 H 7-A-68 A-390 H 4-A-69 A-391 H 5-A-69 A-392 H 6-A-69 A-393 H 7-A-69 A-394 H 4-A-70 A-395 H 5-A-70 A-396 H 6-A-70 A-397 H 7-A-70 A-398 H 4-A-71 A-399 H 5-A-71 A-400 H 6-A-71 A-401 H 7-A-71 A-402 H 4-A-72 A-403 H 5-A-72 A-404 H 6-A-72 A-405 H 7-A-72 A-406 H 4-A-73 A-407 H 5-A-73 A-408 H 6-A-73 A-409 H 7-A-73 A-410 H 4-A-74 A-411 H 5-A-74 A-412 H 6-A-74 A-413 H 7-A-74 A-414 H 4-A-75 A-415 H 5-A-75 A-416 H 6-A-75 A-417 H 7-A-75 A-418 H 4-A-76 A-419 H 5-A-76 A-420 H 6-A-76 A-421 H 7-A-76 A-422 H 4-A-77 A-423 H 5-A-77 A-424 H 6-A-77 A-425 H 7-A-77 A-426 H 4-A-78 A-427 H 5-A-78 A-428 H 6-A-78 A-429 H 7-A-78 A-430 H 4-A-79 A-431 H 5-A-79 A-432 H 6-A-79 A-433 H 7-A-79 A-434 H 4-A-80 A-435 H 5-A-80 A-436 H 6-A-80 A-437 H 7-A-80 A-438 H 4-A-81 A-439 H 5-A-81 A-440 H 6-A-81 A-441 H 7-A-81 A-442 H 4-A-82 A-443 H 5-A-82 A-444 H 6-A-82 A-445 H 7-A-82 A-446 H 4-A-83 A-447 H 5-A-83 A-448 H 6-A-83 A-449 H 7-A-83 A-450 H 4-A-84 A-451 H 5-A-84 A-452 H 6-A-84 A-453 H 7-A-84 A-454 H 4-A-85 A-455 H 5-A-85 A-456 H 6-A-85 A-457 H 7-A-85 A-458 H 4-A-86 A-459 H 5-A-86 A-460 H 6-A-86 A-461 H 7-A-86 A-462 H 4-A-87 A-463 H 5-A-87 A-464 H 6-A-87 A-465 H 7-A-87 A-466 H 4-A-88 A-467 H 5-A-88 A-468 H 6-A-88 A-469 H 7-A-88 A-470 H 4-A-89 A-471 H 5-A-89 A-472 H 6-A-89 A-473 H 7-A-89 A-474 H 4-A-90 A-475 H 5-A-90 A-476 H 6-A-90 A-477 H 7-A-90 A-478 H 4-A-91 A-479 H 5-A-91 A-480 H 6-A-91 A-481 H 7-A-91 A-482 H 4-A-92 A-483 H 5-A-92 A-484 H 6-A-92 A-485 H 7-A-92 A-486 H 4-A-93 A-487 H 5-A-93 A-488 H 6-A-93 A-489 H 7-A-93 A-490 H 4-A-94 A-491 H 5-A-94 A-492 H 6-A-94 A-493 H 7-A-94 A-494 H 4-A-95 A-495 H 5-A-95

A-496 H 6-A-95 A-497 H 7-A-95 A-498 H 4-A-96 A-499 H 5-A-96 A-500 H 6-A-96 A-501 H 7-A-96 A-502 H 4-A-97 A-503 H 5-A-97 A-504 H 6-A-97 A-505 H 7-A-97 A-506 H 4-A-98 A-507 H 5-A-98 A-508 H 6-A-98 A-509 H 7-A-98 A-510 H 4-A-99 A-511 H 5-A-99 A-512 H 6-A-99 A-513 H 7-A-99 A-514 H 4-A-100 A-515 H 5-A-100 A-516 H 6-A-100 A-517 H 7-A-100 A-518 H 4-A-101 A-519 H 5-A-101 A-520 H 6-A-101 A-521 H 7-A-101 A-522 H 4-A-102 A-523 H 5-A-102 A-524 H 6-A-102 A-525 H 7-A-102 A-526 H 4-A-103 A-527 H 5-A-103 A-528 H 6-A-103 A-529 H 7-A-103 A-530 H 4-A-104 A-531 H 5-A-104 A-532 H 6-A-104 A-533 H 7-A-104 A-534 H 4-A-104 A-535 H 5-A-104 A-536 H 6-A-104 A-537 H 7-A-104 A-538 H 4-A-105 A-539 H 5-A-105 A-540 H 6-A-105 A-541 H 7-A-105 A-542 H 4-A-106 A-543 H 5-A-106 A-544 H 6-A-106 A-545 H 7-A-106 A-546 H 4-A-107 A-547 H 5-A-107 A-548 H 6-A-107 A-549 H 7-A-107 A-550 H 4-A-108 A-551 H 5-A-108 A-552 H 6-A-108 A-553 H 7-A-108 A-554 H 4-A-109 A-555 H 5-A-109 A-556 H 6-A-109 A-557 H 7-A-109 A-558 H 4-A-110 A-559 H 5-A-110 A-560 H 6-A-110 A-561 H 7-A-110 A-562 H 4-A-111 A-563 H 5-A-111 A-564 H 6-A-111 A-565 H 7-A-111 A-566 F H A-567 F 4-Cl A-568 F 5-Cl A-569 F 6-Cl A-570 F 7-Cl A-571 F 4-Br A-572 F 5-Br A-573 F 6-Br A-574 F 7-Br A-575 F 4-CN A-576 F 5-CN A-577 F 6-CN A-578 F 7-CN A-579 F 4-OH A-580 F 5-OH A-581 F 6-OH A-582 F 7-OH A-583 F 4-methyl A-584 F 5-methyl A-585 F 6-methyl A-586 F 7-methyl A-587 F 4-ethyl A-588 F 5-ethyl A-589 F 6-ethyl A-590 F 7-ethyl A-591 F 4-propyl A-592 F 5-propyl A-593 F 6-propyl A-594 F 7-propyl A-595 F 4-isopropyl A-596 F 5-isopropyl A-597 F 6-isopropyl A-598 F 7-isopropyl A-599 F 4-hydroxymethyl A-600 F 5-hydroxymethyl A-601 F 6-hydroxymethyl A-602 F 7-hydroxymethyl A-603 F 4-(2-hydroxyethyl) A-604 F 5-(2-hydroxyethyl) A-605 F 6-(2-hydroxyethyl) A-606 F 7-(2-hydroxyethyl) A-607 F 4-(1-hydroxyethyl) A-608 F 5-(1-hydroxyethyl) A-609 F 6-(1-hydroxyethyl) A-610 F 7-(1-hydroxyethyl) A-611 F 4-(3-hydroxypropyl) A-612 F 5-(3-hydroxypropyl) A-613 F 6-(3-hydroxypropyl) A-614 F 7-(3-hydroxypropyl) A-615 F 4-(2-hydroxypropyl) A-616 F 5-(2-hydroxypropyl) A-617 F 6-(2-hydroxypropyl) A-618 F 7-(2-hydroxypropyl) A-619 F 4-(1-hydroxypropyl) A-620 F 5-(1-hydroxypropyl) A-621 F 6-(1-hydroxypropyl) A-622 F 7-(1-hydroxypropyl) A-623 F 4-aminomethyl A-624 F 5-aminomethyl A-625 F 6-aminomethyl A-626 F 7-aminomethyl A-627 F 4-(2-aminoethyl) A-628 F 5-(2-aminoethyl) A-629 F 6-(2-aminoethyl) A-630 F 7-(2-aminoethyl) A-631 F 4-(1-aminoethyl) A-632 F 5-(1-aminoethyl) A-633 F 6-(1-aminoethyl) A-634 F 7-(1-aminoethyl) A-635 F 4-(3-aminopropyl) A-636 F 5-(3-aminopropyl) A-637 F 6-(3-aminopropyl) A-638 F 7-(3-aminopropyl) A-639 F 4-(2-aminopropyl) A-640 F 5-(2-aminopropyl) A-641 F 6-(2-aminopropyl) A-642 F 7-(2-aminopropyl) A-643 F 4-(1-aminopropyl) A-644 F 5-(1-aminopropyl) A-645 F 6-(1-aminopropyl) A-646 F 7-(1-aminopropyl) A-647 F 4-COOH A-648 F 5-COOH A-649 F 6-COOH A-650 F 7-COOH A-651 F 4-COOCH.sub.3 A-652 F 5-COOCH.sub.3 A-653 F 6-COOCH.sub.3 A-654 F 7-COOCH.sub.3 A-655 F 4-COOCH.sub.2CH.sub.3 A-656 F 5-COOCH.sub.2CH.sub.3 A-657 F 6-COOCH.sub.2CH.sub.3 A-658 F 7-COOCH.sub.2CH.sub.3 A-659 F 4-COOCF.sub.3 A-660 F 5-COOCF.sub.3 A-661 F 6-COOCF.sub.3 A-662 F 7-COOCF.sub.3 A-663 F 4-CONH.sub.2 A-664 F 5-CONH.sub.2 A-665 F 6-CONH.sub.2 A-666 F 7-CONH.sub.2 A-667 F 4-CONHCH.sub.3 A-668 F 5-CONHCH.sub.3 A-669 F 6-CONHCH.sub.3 A-670 F 7-CONHCH.sub.3 A-671 F 4-CON(CH.sub.3).sub.2 A-672 F 5-CON(CH.sub.3).sub.2 A-673 F 6-CON(CH.sub.3).sub.2 A-674 F 7-CON(CH.sub.3).sub.2 A-675 F 4-CONHCH.sub.2CH.sub.3 A-676 F 5-CONHCH.sub.2CH.sub.3 A-677 F 6-CONHCH.sub.2CH.sub.3 A-678 F 7-CONHCH.sub.2CH.sub.3 A-679 F 4-CON(CH.sub.2CH.sub.3).sub.2 A-680 F 5-CON(CH.sub.2CH.sub.3).sub.2 A-681 F 6-CON(CH.sub.2CH.sub.3).sub.2 A-682 F 7-CON(CH.sub.2CH.sub.3).sub.2 A-683 F 4-A-1 A-684 F 5-A-1 A-685 F 6-A-1 A-686 F 7-A-1 A-687 F 4-A-2 A-688 F 5-A-2 A-689 F 6-A-2 A-690 F 7-A-2 A-691 F 4-A-3 A-692 F 5-A-3 A-693 F 6-A-3 A-694 F 7-A-3 A-695 F 4-A-4 A-696 F 5-A-4 A-697 F 6-A-4 A-698 F 7-A-4 A-699 F 4-A-5 A-700 F 5-A-5 A-701 F 6-A-5 A-702 F 7-A-5 A-703 F 4-A-6 A-704 F 5-A-6 A-705 F 6-A-6 A-706 F 7-A-6 A-707 F 4-A-7 A-708 F 5-A-7 A-709 F 6-A-7 A-710 F 7-A-7 A-711 F 4-A-8 A-712 F 5-A-8 A-713 F 6-A-8 A-714 F 7-A-8 A-715 F 4-A-9 A-716 F 5-A-9 A-717 F 6-A-9 A-718 F 7-A-9 A-719 F 4-A-10 A-720 F 5-A-10 A-721 F 6-A-10 A-722 F 7-A-10 A-723 F 4-A-11 A-724 F 5-A-11 A-725 F 6-A-11 A-726 F 7-A-11 A-727 F 4-A-12 A-728 F 5-A-12 A-729 F 6-A-12 A-730 F 7-A-12 A-731 F 4-A-13 A-732 F 5-A-13 A-733 F 6-A-13 A-734 F 7-A-13 A-735 F 4-A-14 A-736 F 5-A-14 A-737 F 6-A-14 A-738 F 7-A-14 A-739 F 4-A-15 A-740 F 5-A-15 A-741 F 6-A-15 A-742 F 7-A-15 A-743 F 4-A-16 A-744 F 5-A-16 A-745 F 6-A-16 A-746 F 7-A-16

A-747 F 4-A-17 A-748 F 5-A-17 A-749 F 6-A-17 A-750 F 7-A-17 A-751 F 4-A-18 A-752 F 5-A-18 A-753 F 6-A-18 A-754 F 7-A-18 A-755 F 4-A-19 A-756 F 5-A-19 A-757 F 6-A-19 A-758 F 7-A-19 A-759 F 4-A-20 A-760 F 5-A-20 A-761 F 6-A-20 A-762 F 7-A-20 A-763 F 4-A-21 A-764 F 5-A-21 A-765 F 6-A-21 A-766 F 7-A-21 A-767 F 4-A-22 A-768 F 5-A-22 A-769 F 6-A-22 A-770 F 7-A-22 A-771 F 4-A-23 A-772 F 5-A-23 A-773 F 6-A-23 A-774 F 7-A-23 A-775 F 4-A-24 A-776 F 5-A-24 A-777 F 6-A-24 A-778 F 7-A-24 A-779 F 4-A-25 A-780 F 5-A-25 A-781 F 6-A-25 A-782 F 7-A-25 A-783 F 4-A-26 A-784 F 5-A-26 A-785 F 6-A-26 A-786 F 7-A-26 A-787 F 4-A-27 A-788 F 5-A-27 A-789 F 6-A-27 A-790 F 7-A-27 A-791 F 4-A-28 A-792 F 5-A-28 A-793 F 6-A-28 A-794 F 7-A-28 A-795 F 4-A-29 A-796 F 5-A-29 A-797 F 6-A-29 A-798 F 7-A-29 A-799 F 4-A-30 A-800 F 5-A-30 A-801 F 6-A-30 A-802 F 7-A-30 A-803 F 4-A-31 A-804 F 5-A-31 A-805 F 6-A-31 A-806 F 7-A-31 A-807 F 4-A-32 A-808 F 5-A-32 A-809 F 6-A-32 A-810 F 7-A-32 A-811 F 4-A-33 A-812 F 5-A-33 A-813 F 6-A-33 A-814 F 7-A-33 A-815 F 4-A-34 A-816 F 5-A-34 A-817 F 6-A-34 A-818 F 7-A-34 A-819 F 4-A-35 A-820 F 5-A-35 A-821 F 6-A-35 A-822 F 7-A-35 A-823 F 4-A-36 A-824 F 5-A-36 A-825 F 6-A-36 A-826 F 7-A-36 A-827 F 4-A-37 A-828 F 5-A-37 A-829 F 6-A-37 A-830 F 7-A-37 A-831 F 4-A-38 A-832 F 5-A-38 A-833 F 6-A-38 A-834 F 7-A-38 A-835 F 4-A-39 A-836 F 5-A-39 A-837 F 6-A-39 A-838 F 7-A-39 A-839 F 4-A-40 A-840 F 5-A-40 A-841 F 6-A-40 A-842 F 7-A-40 A-843 F 4-A-41 A-844 F 5-A-41 A-845 F 6-A-41 A-846 F 7-A-41 A-847 F 4-A-42 A-848 F 5-A-42 A-849 F 6-A-42 A-850 F 7-A-42 A-851 F 4-A-43 A-852 F 5-A-43 A-853 F 6-A-43 A-854 F 7-A-43 A-855 F 4-A-44 A-856 F 5-A-44 A-857 F 6-A-44 A-858 F 7-A-44 A-859 F 4-A-45 A-860 F 5-A-45 A-861 F 6-A-45 A-862 F 7-A-45 A-863 F 4-A-46 A-864 F 5-A-46 A-865 F 6-A-46 A-866 F 7-A-46 A-867 F 4-A-47 A-868 F 5-A-47 A-869 F 6-A-47 A-870 F 7-A-47 A-871 F 4-A-48 A-872 F 5-A-48 A-873 F 6-A-48 A-874 F 7-A-48 A-875 F 4-A-49 A-876 F 5-A-49 A-877 F 6-A-49 A-878 F 7-A-49 A-879 F 4-A-50 A-880 F 5-A-50 A-881 F 6-A-50 A-882 F 7-A-50 A-883 F 4-A-51 A-884 F 5-A-51 A-885 F 6-A-51 A-886 F 7-A-51 A-887 F 4-A-52 A-888 F 5-A-52 A-889 F 6-A-52 A-890 F 7-A-52 A-891 F 4-A-53 A-892 F 5-A-53 A-893 F 6-A-53 A-894 F 7-A-53 A-895 F 4-A-54 A-896 F 5-A-54 A-897 F 6-A-54 A-898 F 7-A-54 A-899 F 4-A-55 A-900 F 5-A-55 A-901 F 6-A-55 A-902 F 7-A-55 A-903 F 4-A-56 A-904 F 5-A-56 A-905 F 6-A-56 A-906 F 7-A-56 A-907 F 4-A-57 A-908 F 5-A-57 A-909 F 6-A-57 A-910 F 7-A-57 A-911 F 4-A-58 A-912 F 5-A-58 A-913 F 6-A-58 A-914 F 7-A-58 A-915 F 4-A-59 A-916 F 5-A-59 A-917 F 6-A-59 A-918 F 7-A-59 A-919 F 4-A-60 A-920 F 5-A-60 A-921 F 6-A-60 A-922 F 7-A-60 A-923 F 4-A-61 A-924 F 5-A-61 A-925 F 6-A-61 A-926 F 7-A-61 A-927 F 4-A-62 A-928 F 5-A-62 A-929 F 6-A-62 A-930 F 7-A-62 A-931 F 4-A-63 A-932 F 5-A-63 A-933 F 6-A-63 A-934 F 7-A-63 A-935 F 4-A-64 A-936 F 5-A-64 A-937 F 6-A-64 A-938 F 7-A-64 A-939 F 4-A-65 A-940 F 5-A-65 A-941 F 6-A-65 A-942 F 7-A-65 A-943 F 4-A-66 A-944 F 5-A-66 A-945 F 6-A-66 A-946 F 7-A-66 A-947 F 4-A-67 A-948 F 5-A-67 A-949 F 6-A-67 A-950 F 7-A-67 A-951 F 4-A-68 A-952 F 5-A-68 A-953 F 6-A-68 A-954 F 7-A-68 A-955 F 4-A-69 A-956 F 5-A-69 A-957 F 6-A-69 A-958 F 7-A-69 A-959 F 4-A-70 A-960 F 5-A-70 A-961 F 6-A-70 A-962 F 7-A-70 A-963 F 4-A-71 A-964 F 5-A-71 A-965 F 6-A-71 A-966 F 7-A-71 A-967 F 4-A-72 A-968 F 5-A-72 A-969 F 6-A-72 A-970 F 7-A-72 A-971 F 4-A-73 A-972 F 5-A-73 A-973 F 6-A-73 A-974 F 7-A-73 A-975 F 4-A-74 A-976 F 5-A-74 A-977 F 6-A-74 A-978 F 7-A-74 A-979 F 4-A-75 A-980 F 5-A-75 A-981 F 6-A-75 A-982 F 7-A-75 A-983 F 4-A-76 A-984 F 5-A-76 A-985 F 6-A-76 A-986 F 7-A-76 A-987 F 4-A-77 A-988 F 5-A-77 A-989 F 6-A-77 A-990 F 7-A-77 A-991 F 4-A-78 A-992 F 5-A-78 A-993 F 6-A-78 A-994 F 7-A-78 A-995 F 4-A-79 A-996 F 5-A-79 A-997 F 6-A-79

A-998 F 7-A-79 A-999 F 4-A-80 A-1000 F 5-A-80 A-1001 F 6-A-80 A-1002 F 7-A-80 A-1003 F 4-A-81 A-1004 F 5-A-81 A-1005 F 6-A-81 A-1006 F 7-A-81 A-1007 F 4-A-82 A-1008 F 5-A-82 A-1009 F 6-A-82 A-1010 F 7-A-82 A-1011 F 4-A-83 A-1012 F 5-A-83 A-1013 F 6-A-83 A-1014 F 7-A-83 A-1015 F 4-A-84 A-1016 F 5-A-84 A-1017 F 6-A-84 A-1018 F 7-A-84 A-1019 F 4-A-85 A-1020 F 5-A-85 A-1021 F 6-A-85 A-1022 F 7-A-85 A-1023 F 4-A-86 A-1024 F 5-A-86 A-1025 F 6-A-86 A-1026 F 7-A-86 A-1027 F 4-A-87 A-1028 F 5-A-87 A-1029 F 6-A-87 A-1030 F 7-A-87 A-1031 F 4-A-88 A-1032 F 5-A-88 A-1033 F 6-A-88 A-1034 F 7-A-88 A-1035 F 4-A-89 A-1036 F 5-A-89 A-1037 F 6-A-89 A-1038 F 7-A-89 A-1039 F 4-A-90 A-1040 F 5-A-90 A-1041 F 6-A-90 A-1042 F 7-A-90 A-1043 F 4-A-91 A-1044 F 5-A-91 A-1045 F 6-A-91 A-1046 F 7-A-91 A-1047 F 4-A-92 A-1048 F 5-A-92 A-1049 F 6-A-92 A-1050 F 7-A-92 A-1051 F 4-A-93 A-1052 F 5-A-93 A-1053 F 6-A-93 A-1054 F 7-A-93 A-1055 F 4-A-94 A-1056 F 5-A-94 A-1057 F 6-A-94 A-1058 F 7-A-94 A-1059 F 4-A-95 A-1060 F 5-A-95 A-1061 F 6-A-95 A-1062 F 7-A-95 A-1063 F 4-A-96 A-1064 F 5-A-96 A-1065 F 6-A-96 A-1066 F 7-A-96 A-1067 F 4-A-97 A-1068 F 5-A-97 A-1069 F 6-A-97 A-1070 F 7-A-97 A-1071 F 4-A-98 A-1072 F 5-A-98 A-1073 F 6-A-98 A-1074 F 7-A-98 A-1075 F 4-A-99 A-1076 F 5-A-99 A-1077 F 6-A-99 A-1078 F 7-A-99 A-1079 F 4-A-100 A-1080 F 5-A-100 A-1081 F 6-A-100 A-1082 F 7-A-100 A-1083 F 4-A-101 A-1084 F 5-A-101 A-1085 F 6-A-101 A-1086 F 7-A-101 A-1087 F 4-A-102 A-1088 F 5-A-102 A-1089 F 6-A-102 A-1090 F 7-A-102 A-1091 F 4-A-103 A-1092 F 5-A-103 A-1093 F 6-A-103 A-1094 F 7-A-103 A-1095 F 4-A-104 A-1096 F 5-A-104 A-1097 F 6-A-104 A-1098 F 7-A-104 A-1099 F 4-A-104 A-1100 F 5-A-104 A-1101 F 6-A-104 A-1102 F 7-A-104 A-1103 F 4-A-105 A-1104 F 5-A-105 A-1105 F 6-A-105 A-1106 F 7-A-105 A-1107 F 4-A-106 A-1108 F 5-A-106 A-1109 F 6-A-106 A-1110 F 7-A-106 A-1111 F 4-A-107 A-1112 F 5-A-107 A-1113 F 6-A-107 A-1114 F 7-A-107 A-1115 F 4-A-108 A-1116 F 5-A-108 A-1117 F 6-A-108 A-1118 F 7-A-108 A-1119 F 4-A-109 A-1120 F 5-A-109 A-1121 F 6-A-109 A-1122 F 7-A-109 A-1123 F 4-A-110 A-1124 F 5-A-110 A-1125 F 6-A-110 A-1126 F 7-A-110 A-1127 F 4-A-111 A-1128 F 5-A-111 A-1129 F 6-A-111 A-1130 F 7-A-111 A-1131 allyl H A-1132 allyl 4-Cl A-1133 allyl 5-Cl A-1134 allyl 6-Cl A-1135 allyl 7-Cl A-1136 allyl 4-Br A-1137 allyl 5-Br A-1138 allyl 6-Br A-1139 allyl 7-Br A-1140 allyl 4-CN A-1141 allyl 5-CN A-1142 allyl 6-CN A-1143 allyl 7-CN A-1144 allyl 4-OH A-1145 allyl 5-OH A-1146 allyl 6-OH A-1147 allyl 7-OH A-1148 allyl 4-methyl A-1149 allyl 5-methyl A-1150 allyl 6-methyl A-1151 allyl 7-methyl A-1152 allyl 4-ethyl A-1153 allyl 5-ethyl A-1154 allyl 6-ethyl A-1155 allyl 7-ethyl A-1156 allyl 4-propyl A-1157 allyl 5-propyl A-1158 allyl 6-propyl A-1159 allyl 7-propyl A-1160 allyl 4-isopropyl A-1161 allyl 5-isopropyl A-1162 allyl 6-isopropyl A-1163 allyl 7-isopropyl A-1164 allyl 4-hydroxymethyl A-1165 allyl 5-hydroxymethyl A-1166 allyl 6-hydroxymethyl A-1167 allyl 7-hydroxymethyl A-1168 allyl 4-(2-hydroxyethyl) A-1169 allyl 5-(2-hydroxyethyl) A-1170 allyl 6-(2-hydroxyethyl) A-1171 allyl 7-(2-hydroxyethyl) A-1172 allyl 4-(1-hydroxyethyl) A-1173 allyl 5-(1-hydroxyethyl) A-1174 allyl 6-(1-hydroxyethyl) A-1175 allyl 7-(1-hydroxyethyl) A-1176 allyl 4-(3-hydroxypropyl) A-1177 allyl 5-(3-hydroxypropyl) A-1178 allyl 6-(3-hydroxypropyl) A-1179 allyl 7-(3-hydroxypropyl) A-1180 allyl 4-(2-hydroxypropyl) A-1181 allyl 5-(2-hydroxypropyl) A-1182 allyl 6-(2-hydroxypropyl) A-1183 allyl 7-(2-hydroxypropyl) A-1184 allyl 4-(1-hydroxypropyl) A-1185 allyl 5-(1-hydroxypropyl) A-1186 allyl 6-(1-hydroxypropyl) A-1187 allyl 7-(1-hydroxypropyl) A-1188 allyl 4-aminomethyl A-1189 allyl 5-aminomethyl A-1190 allyl 6-aminomethyl A-1191 allyl 7-aminomethyl A-1192 allyl 4-(2-aminoethyl) A-1193 allyl 5-(2-aminoethyl) A-1194 allyl 6-(2-aminoethyl) A-1195 allyl 7-(2-aminoethyl) A-1196 allyl 4-(1-aminoethyl) A-1197 allyl 5-(1-aminoethyl) A-1198 allyl 6-(1-aminoethyl) A-1199 allyl 7-(1-aminoethyl) A-1200 allyl 4-(3-aminopropyl) A-1201 allyl 5-(3-aminopropyl) A-1202 allyl 6-(3-aminopropyl) A-1203 allyl 7-(3-aminopropyl) A-1204 allyl 4-(2-aminopropyl) A-1205 allyl 5-(2-aminopropyl) A-1206 allyl 6-(2-aminopropyl) A-1207 allyl 7-(2-aminopropyl) A-1208 allyl 4-(1-aminopropyl) A-1209 allyl 5-(1-aminopropyl) A-1210 allyl 6-(1-aminopropyl) A-1211 allyl 7-(1-aminopropyl) A-1212 allyl 4-COOH A-1213 allyl 5-COOH A-1214 allyl 6-COOH A-1215 allyl 7-COOH A-1216 allyl 4-COOCH.sub.3 A-1217 allyl 5-COOCH.sub.3 A-1218 allyl 6-COOCH.sub.3 A-1219 allyl 7-COOCH.sub.3 A-1220 allyl 4-COOCH.sub.2CH.sub.3 A-1221 allyl 5-COOCH.sub.2CH.sub.3 A-1222 allyl 6-COOCH.sub.2CH.sub.3 A-1223 allyl 7-COOCH.sub.2CH.sub.3 A-1224 allyl 4-COOCF.sub.3 A-1225 allyl 5-COOCF.sub.3 A-1226 allyl 6-COOCF.sub.3 A-1227 allyl 7-COOCF.sub.3 A-1228 allyl 4-CONH.sub.2 A-1229 allyl 5-CONH.sub.2 A-1230 allyl 6-CONH.sub.2 A-1231 allyl 7-CONH.sub.2 A-1232 allyl 4-CONHCH.sub.3 A-1233 allyl 5-CONHCH.sub.3 A-1234 allyl 6-CONHCH.sub.3 A-1235 allyl 7-CONHCH.sub.3 A-1236 allyl 4-CON(CH.sub.3).sub.2 A-1237 allyl 5-CON(CH.sub.3).sub.2 A-1238 allyl 6-CON(CH.sub.3).sub.2 A-1239 allyl 7-CON(CH.sub.3).sub.2 A-1240 allyl 4-CONHCH.sub.2CH.sub.3 A-1241 allyl 5-CONHCH.sub.2CH.sub.3 A-1242 allyl 6-CONHCH.sub.2CH.sub.3 A-1243 allyl 7-CONHCH.sub.2CH.sub.3 A-1244 allyl 4-CON(CH.sub.2CH.sub.3).sub.2 A-1245 allyl 5-CON(CH.sub.2CH.sub.3).sub.2 A-1246 allyl 6-CON(CH.sub.2CH.sub.3).sub.2 A-1247 allyl 7-CON(CH.sub.2CH.sub.3).sub.2 A-1248 allyl 4-A-1

A-1249 allyl 5-A-1 A-1250 allyl 6-A-1 A-1251 allyl 7-A-1 A-1252 allyl 4-A-2 A-1253 allyl 5-A-2 A-1254 allyl 6-A-2 A-1255 allyl 7-A-2 A-1256 allyl 4-A-3 A-1257 allyl 5-A-3 A-1258 allyl 6-A-3 A-1259 allyl 7-A-3 A-1260 allyl 4-A-4 A-1261 allyl 5-A-4 A-1262 allyl 6-A-4 A-1263 allyl 7-A-4 A-1264 allyl 4-A-5 A-1265 allyl 5-A-5 A-1266 allyl 6-A-5 A-1267 allyl 7-A-5 A-1268 allyl 4-A-6 A-1269 allyl 5-A-6 A-1270 allyl 6-A-6 A-1271 allyl 7-A-6 A-1272 allyl 4-A-7 A-1273 allyl 5-A-7 A-1274 allyl 6-A-7 A-1275 allyl 7-A-7 A-1276 allyl 4-A-8 A-1277 allyl 5-A-8 A-1278 allyl 6-A-8 A-1279 allyl 7-A-8 A-1280 allyl 4-A-9 A-1281 allyl 5-A-9 A-1282 allyl 6-A-9 A-1283 allyl 7-A-9 A-1284 allyl 4-A-10 A-1285 allyl 5-A-10 A-1286 allyl 6-A-10 A-1287 allyl 7-A-10 A-1288 allyl 4-A-11 A-1289 allyl 5-A-11 A-1290 allyl 6-A-11 A-1291 allyl 7-A-11 A-1292 allyl 4-A-12 A-1293 allyl 5-A-12 A-1294 allyl 6-A-12 A-1295 allyl 7-A-12 A-1296 allyl 4-A-13 A-1297 allyl 5-A-13 A-1298 allyl 6-A-13 A-1299 allyl 7-A-13 A-1300 allyl 4-A-14 A-1301 allyl 5-A-14 A-1302 allyl 6-A-14 A-1303 allyl 7-A-14 A-1304 allyl 4-A-15 A-1305 allyl 5-A-15 A-1306 allyl 6-A-15 A-1307 allyl 7-A-15 A-1308 allyl 4-A-16 A-1309 allyl 5-A-16 A-1310 allyl 6-A-16 A-1311 allyl 7-A-16 A-1312 allyl 4-A-17 A-1313 allyl 5-A-17 A-1314 allyl 6-A-17 A-1315 allyl 7-A-17 A-1316 allyl 4-A-18 A-1317 allyl 5-A-18 A-1318 allyl 6-A-18 A-1319 allyl 7-A-18 A-1320 allyl 4-A-19 A-1321 allyl 5-A-19 A-1322 allyl 6-A-19 A-1323 allyl 7-A-19 A-1324 allyl 4-A-20 A-1325 allyl 5-A-20 A-1326 allyl 6-A-20 A-1327 allyl 7-A-20 A-1328 allyl 4-A-21 A-1329 allyl 5-A-21 A-1330 allyl 6-A-21 A-1331 allyl 7-A-21 A-1332 allyl 4-A-22 A-1333 allyl 5-A-22 A-1334 allyl 6-A-22 A-1335 allyl 7-A-22 A-1336 allyl 4-A-23 A-1337 allyl 5-A-23 A-1338 allyl 6-A-23 A-1339 allyl 7-A-23 A-1340 allyl 4-A-24 A-1341 allyl 5-A-24 A-1342 allyl 6-A-24 A-1343 allyl 7-A-24 A-1344 allyl 4-A-25 A-1345 allyl 5-A-25 A-1346 allyl 6-A-25 A-1347 allyl 7-A-25 A-1348 allyl 4-A-26 A-1349 allyl 5-A-26 A-1350 allyl 6-A-26 A-1351 allyl 7-A-26 A-1352 allyl 4-A-27 A-1353 allyl 5-A-27 A-1354 allyl 6-A-27 A-1355 allyl 7-A-27 A-1356 allyl 4-A-28 A-1357 allyl 5-A-28 A-1358 allyl 6-A-28 A-1359 allyl 7-A-28 A-1360 allyl 4-A-29 A-1361 allyl 5-A-29 A-1362 allyl 6-A-29 A-1363 allyl 7-A-29 A-1364 allyl 4-A-30 A-1365 allyl 5-A-30 A-1366 allyl 6-A-30 A-1367 allyl 7-A-30 A-1368 allyl 4-A-31 A-1369 allyl 5-A-31 A-1370 allyl 6-A-31 A-1371 allyl 7-A-31 A-1372 allyl 4-A-32 A-1373 allyl 5-A-32 A-1374 allyl 6-A-32 A-1375 allyl 7-A-32 A-1376 allyl 4-A-33 A-1377 allyl 5-A-33 A-1378 allyl 6-A-33 A-1379 allyl 7-A-33 A-1380 allyl 4-A-34 A-1381 allyl 5-A-34 A-1382 allyl 6-A-34 A-1383 allyl 7-A-34 A-1384 allyl 4-A-35 A-1385 allyl 5-A-35 A-1386 allyl 6-A-35 A-1387 allyl 7-A-35 A-1388 allyl 4-A-36 A-1389 allyl 5-A-36 A-1390 allyl 6-A-36 A-1391 allyl 7-A-36 A-1392 allyl 4-A-37 A-1393 allyl 5-A-37 A-1394 allyl 6-A-37 A-1395 allyl 7-A-37 A-1396 allyl 4-A-38 A-1397 allyl 5-A-38 A-1398 allyl 6-A-38 A-1399 allyl 7-A-38 A-1400 allyl 4-A-39 A-1401 allyl 5-A-39 A-1402 allyl 6-A-39 A-1403 allyl 7-A-39 A-1404 allyl 4-A-40 A-1405 allyl 5-A-40 A-1406 allyl 6-A-40 A-1407 allyl 7-A-40 A-1408 allyl 4-A-41 A-1409 allyl 5-A-41 A-1410 allyl 6-A-41 A-1411 allyl 7-A-41 A-1412 allyl 4-A-42 A-1413 allyl 5-A-42 A-1414 allyl 6-A-42 A-1415 allyl 7-A-42 A-1416 allyl 4-A-43 A-1417 allyl 5-A-43 A-1418 allyl 6-A-43 A-1419 allyl 7-A-43 A-1420 allyl 4-A-44 A-1421 allyl 5-A-44 A-1422 allyl 6-A-44 A-1423 allyl 7-A-44 A-1424 allyl 4-A-45 A-1425 allyl 5-A-45 A-1426 allyl 6-A-45 A-1427 allyl 7-A-45 A-1428 allyl 4-A-46 A-1429 allyl 5-A-46 A-1430 allyl 6-A-46 A-1431 allyl 7-A-46 A-1432 allyl 4-A-47 A-1433 allyl 5-A-47 A-1434 allyl 6-A-47 A-1435 allyl 7-A-47 A-1436 allyl 4-A-48 A-1437 allyl 5-A-48 A-1438 allyl 6-A-48 A-1439 allyl 7-A-48 A-1440 allyl 4-A-49 A-1441 allyl 5-A-49 A-1442 allyl 6-A-49 A-1443 allyl 7-A-49 A-1444 allyl 4-A-50 A-1445 allyl 5-A-50 A-1446 allyl 6-A-50 A-1447 allyl 7-A-50 A-1448 allyl 4-A-51 A-1449 allyl 5-A-51 A-1450 allyl 6-A-51 A-1451 allyl 7-A-51 A-1452 allyl 4-A-52 A-1453 allyl 5-A-52 A-1454 allyl 6-A-52 A-1455 allyl 7-A-52 A-1456 allyl 4-A-53 A-1457 allyl 5-A-53 A-1458 allyl 6-A-53 A-1459 allyl 7-A-53 A-1460 allyl 4-A-54 A-1461 allyl 5-A-54 A-1462 allyl 6-A-54 A-1463 allyl 7-A-54 A-1464 allyl 4-A-55 A-1465 allyl 5-A-55 A-1466 allyl 6-A-55 A-1467 allyl 7-A-55 A-1468 allyl 4-A-56 A-1469 allyl 5-A-56 A-1470 allyl 6-A-56 A-1471 allyl 7-A-56 A-1472 allyl 4-A-57 A-1473 allyl 5-A-57 A-1474 allyl 6-A-57 A-1475 allyl 7-A-57 A-1476 allyl 4-A-58 A-1477 allyl 5-A-58 A-1478 allyl 6-A-58 A-1479 allyl 7-A-58 A-1480 allyl 4-A-59 A-1481 allyl 5-A-59 A-1482 allyl 6-A-59 A-1483 allyl 7-A-59 A-1484 allyl 4-A-60 A-1485 allyl 5-A-60 A-1486 allyl 6-A-60 A-1487 allyl 7-A-60 A-1488 allyl 4-A-61 A-1489 allyl 5-A-61 A-1490 allyl 6-A-61 A-1491 allyl 7-A-61 A-1492 allyl 4-A-62 A-1493 allyl 5-A-62 A-1494 allyl 6-A-62 A-1495 allyl 7-A-62 A-1496 allyl 4-A-63 A-1497 allyl 5-A-63 A-1498 allyl 6-A-63 A-1499 allyl 7-A-63

A-1500 allyl 4-A-64 A-1501 allyl 5-A-64 A-1502 allyl 6-A-64 A-1503 allyl 7-A-64 A-1504 allyl 4-A-65 A-1505 allyl 5-A-65 A-1506 allyl 6-A-65 A-1507 allyl 7-A-65 A-1508 allyl 4-A-66 A-1509 allyl 5-A-66 A-1510 allyl 6-A-66 A-1511 allyl 7-A-66 A-1512 allyl 4-A-67 A-1513 allyl 5-A-67 A-1514 allyl 6-A-67 A-1515 allyl 7-A-67 A-1516 allyl 4-A-68 A-1517 allyl 5-A-68 A-1518 allyl 6-A-68 A-1519 allyl 7-A-68 A-1520 allyl 4-A-69 A-1521 allyl 5-A-69 A-1522 allyl 6-A-69 A-1523 allyl 7-A-69 A-1524 allyl 4-A-70 A-1525 allyl 5-A-70 A-1526 allyl 6-A-70 A-1527 allyl 7-A-70 A-1528 allyl 4-A-71 A-1529 allyl 5-A-71 A-1530 allyl 6-A-71 A-1531 allyl 7-A-71 A-1532 allyl 4-A-72 A-1533 allyl 5-A-72 A-1534 allyl 6-A-72 A-1535 allyl 7-A-72 A-1536 allyl 4-A-73 A-1537 allyl 5-A-73 A-1538 allyl 6-A-73 A-1539 allyl 7-A-73 A-1540 allyl 4-A-74 A-1541 allyl 5-A-74 A-1542 allyl 6-A-74 A-1543 allyl 7-A-74 A-1544 allyl 4-A-75 A-1545 allyl 5-A-75 A-1546 allyl 6-A-75 A-1547 allyl 7-A-75 A-1548 allyl 4-A-76 A-1549 allyl 5-A-76 A-1550 allyl 6-A-76 A-1551 allyl 7-A-76 A-1552 allyl 4-A-77 A-1553 allyl 5-A-77 A-1554 allyl 6-A-77 A-1555 allyl 7-A-77 A-1556 allyl 4-A-78 A-1557 allyl 5-A-78 A-1558 allyl 6-A-78 A-1559 allyl 7-A-78 A-1560 allyl 4-A-79 A-1561 allyl 5-A-79 A-1562 allyl 6-A-79 A-1563 allyl 7-A-79 A-1564 allyl 4-A-80 A-1565 allyl 5-A-80 A-1566 allyl 6-A-80 A-1567 allyl 7-A-80 A-1568 allyl 4-A-81 A-1569 allyl 5-A-81 A-1570 allyl 6-A-81 A-1571 allyl 7-A-81 A-1572 allyl 4-A-82 A-1573 allyl 5-A-82 A-1574 allyl 6-A-82 A-1575 allyl 7-A-82 A-1576 allyl 4-A-83 A-1577 allyl 5-A-83 A-1578 allyl 6-A-83 A-1579 allyl 7-A-83 A-1580 allyl 4-A-84 A-1581 allyl 5-A-84 A-1582 allyl 6-A-84 A-1583 allyl 7-A-84 A-1584 allyl 4-A-85 A-1585 allyl 5-A-85 A-1586 allyl 6-A-85 A-1587 allyl 7-A-85 A-1588 allyl 4-A-86 A-1589 allyl 5-A-86 A-1590 allyl 6-A-86 A-1591 allyl 7-A-86 A-1592 allyl 4-A-87 A-1593 allyl 5-A-87 A-1594 allyl 6-A-87 A-1595 allyl 7-A-87 A-1596 allyl 4-A-88 A-1597 allyl 5-A-88 A-1598 allyl 6-A-88 A-1599 allyl 7-A-88 A-1600 allyl 4-A-89 A-1601 allyl 5-A-89 A-1602 allyl 6-A-89 A-1603 allyl 7-A-89 A-1604 allyl 4-A-90 A-1605 allyl 5-A-90 A-1606 allyl 6-A-90 A-1607 allyl 7-A-90 A-1608 allyl 4-A-91 A-1609 allyl 5-A-91 A-1610 allyl 6-A-91 A-1611 allyl 7-A-91 A-1612 allyl 4-A-92 A-1613 allyl 5-A-92 A-1614 allyl 6-A-92 A-1615 allyl 7-A-92 A-1616 allyl 4-A-93 A-1617 allyl 5-A-93 A-1618 allyl 6-A-93 A-1619 allyl 7-A-93 A-1620 allyl 4-A-94 A-1621 allyl 5-A-94 A-1622 allyl 6-A-94 A-1623 allyl 7-A-94 A-1624 allyl 4-A-95 A-1625 allyl 5-A-95 A-1626 allyl 6-A-95 A-1627 allyl 7-A-95 A-1628 allyl 4-A-96 A-1629 allyl 5-A-96 A-1630 allyl 6-A-96 A-1631 allyl 7-A-96 A-1632 allyl 4-A-97 A-1633 allyl 5-A-97 A-1634 allyl 6-A-97 A-1635 allyl 7-A-97 A-1636 allyl 4-A-98 A-1637 allyl 5-A-98 A-1638 allyl 6-A-98 A-1639 allyl 7-A-98 A-1640 allyl 4-A-99 A-1641 allyl 5-A-99 A-1642 allyl 6-A-99 A-1643 allyl 7-A-99 A-1644 allyl 4-A-100 A-1645 allyl 5-A-100 A-1646 allyl 6-A-100 A-1647 allyl 7-A-100 A-1648 allyl 4-A-101 A-1649 allyl 5-A-101 A-1650 allyl 6-A-101 A-1651 allyl 7-A-101 A-1652 allyl 4-A-102 A-1653 allyl 5-A-102 A-1654 allyl 6-A-102 A-1655 allyl 7-A-102 A-1656 allyl 4-A-103 A-1657 allyl 5-A-103 A-1658 allyl 6-A-103 A-1659 allyl 7-A-103 A-1660 allyl 4-A-104 A-1661 allyl 5-A-104 A-1662 allyl 6-A-104 A-1663 allyl 7-A-104 A-1664 allyl 4-A-104 A-1665 allyl 5-A-104 A-1666 allyl 6-A-104 A-1667 allyl 7-A-104 A-1668 allyl 4-A-105 A-1669 allyl 5-A-105 A-1670 allyl 6-A-105 A-1671 allyl 7-A-105 A-1672 allyl 4-A-106 A-1673 allyl 5-A-106 A-1674 allyl 6-A-106 A-1675 allyl 7-A-106 A-1676 allyl 4-A-107 A-1677 allyl 5-A-107 A-1678 allyl 6-A-107 A-1679 allyl 7-A-107 A-1680 allyl 4-A-108 A-1681 allyl 5-A-108 A-1682 allyl 6-A-108 A-1683 allyl 7-A-108 A-1684 allyl 4-A-109 A-1685 allyl 5-A-109 A-1686 allyl 6-A-109 A-1687 allyl 7-A-109 A-1688 allyl 4-A-110 A-1689 allyl 5-A-110 A-1690 allyl 6-A-110 A-1691 allyl 7-A-110 A-1692 allyl 4-A-111 A-1693 allyl 5-A-111 A-1694 allyl 6-A-111 A-1695 allyl 7-A-111 A-1696 CH.sub.2CHF.sub.2 H A-1697 CH.sub.2CHF.sub.2 4-Cl A-1698 CH.sub.2CHF.sub.2 5-Cl A-1699 CH.sub.2CHF.sub.2 6-Cl A-1700 CH.sub.2CHF.sub.2 7-Cl A-1701 CH.sub.2CHF.sub.2 4-Br A-1702 CH.sub.2CHF.sub.2 5-Br A-1703 CH.sub.2CHF.sub.2 6-Br A-1704 CH.sub.2CHF.sub.2 7-Br A-1705 CH.sub.2CHF.sub.2 4-CN A-1706 CH.sub.2CHF.sub.2 5-CN A-1707 CH.sub.2CHF.sub.2 6-CN A-1708 CH.sub.2CHF.sub.2 7-CN A-1709 CH.sub.2CHF.sub.2 4-OH A-1710 CH.sub.2CHF.sub.2 5-OH A-1711 CH.sub.2CHF.sub.2 6-OH A-1712 CH.sub.2CHF.sub.2 7-OH A-1713 CH.sub.2CHF.sub.2 4-methyl A-1714 CH.sub.2CHF.sub.2 5-methyl A-1715 CH.sub.2CHF.sub.2 6-methyl A-1716 CH.sub.2CHF.sub.2 7-methyl A-1717 CH.sub.2CHF.sub.2 4-ethyl A-1718 CH.sub.2CHF.sub.2 5-ethyl A-1719 CH.sub.2CHF.sub.2 6-ethyl A-1720 CH.sub.2CHF.sub.2 7-ethyl A-1721 CH.sub.2CHF.sub.2 4-propyl A-1722 CH.sub.2CHF.sub.2 5-propyl A-1723 CH.sub.2CHF.sub.2 6-propyl A-1724 CH.sub.2CHF.sub.2 7-propyl A-1725 CH.sub.2CHF.sub.2 4-isopropyl A-1726 CH.sub.2CHF.sub.2 5-isopropyl A-1727 CH.sub.2CHF.sub.2 6-isopropyl A-1728 CH.sub.2CHF.sub.2 7-isopropyl A-1729 CH.sub.2CHF.sub.2 4-hydroxymethyl A-1730 CH.sub.2CHF.sub.2 5-hydroxymethyl A-1731 CH.sub.2CHF.sub.2 6-hydroxymethyl A-1732 CH.sub.2CHF.sub.2 7-hydroxymethyl A-1733 CH.sub.2CHF.sub.2 4-(2-hydroxyethyl) A-1734 CH.sub.2CHF.sub.2 5-(2-hydroxyethyl) A-1735 CH.sub.2CHF.sub.2 6-(2-hydroxyethyl) A-1736 CH.sub.2CHF.sub.2 7-(2-hydroxyethyl) A-1737 CH.sub.2CHF.sub.2 4-(1-hydroxyethyl) A-1738 CH.sub.2CHF.sub.2 5-(1-hydroxyethyl) A-1739 CH.sub.2CHF.sub.2 6-(1-hydroxyethyl) A-1740 CH.sub.2CHF.sub.2 7-(1-hydroxyethyl) A-1741 CH.sub.2CHF.sub.2 4-(3-hydroxypropyl) A-1742 CH.sub.2CHF.sub.2 5-(3-hydroxypropyl) A-1743 CH.sub.2CHF.sub.2 6-(3-hydroxypropyl) A-1744 CH.sub.2CHF.sub.2 7-(3-hydroxypropyl) A-1745 CH.sub.2CHF.sub.2 4-(2-hydroxypropyl) A-1746 CH.sub.2CHF.sub.2 5-(2-hydroxypropyl) A-1747 CH.sub.2CHF.sub.2 6-(2-hydroxypropyl) A-1748 CH.sub.2CHF.sub.2 7-(2-hydroxypropyl) A-1749 CH.sub.2CHF.sub.2 4-(1-hydroxypropyl) A-1750 CH.sub.2CHF.sub.2 5-(1-hydroxypropyl)

A-1751 CH.sub.2CHF.sub.2 6-(1-hydroxypropyl) A-1752 CH.sub.2CHF.sub.2 7-(1-hydroxypropyl) A-1753 CH.sub.2CHF.sub.2 4-aminomethyl A-1754 CH.sub.2CHF.sub.2 5-aminomethyl A-1755 CH.sub.2CHF.sub.2 6-aminomethyl A-1756 CH.sub.2CHF.sub.2 7-aminomethyl A-1757 CH.sub.2CHF.sub.2 4-(2-aminoethyl) A-1758 CH.sub.2CHF.sub.2 5-(2-aminoethyl) A-1759 CH.sub.2CHF.sub.2 6-(2-aminoethyl) A-1760 CH.sub.2CHF.sub.2 7-(2-aminoethyl) A-1761 CH.sub.2CHF.sub.2 4-(1-aminoethyl) A-1762 CH.sub.2CHF.sub.2 5-(1-aminoethyl) A-1763 CH.sub.2CHF.sub.2 6-(1-aminoethyl) A-1764 CH.sub.2CHF.sub.2 7-(1-aminoethyl) A-1765 CH.sub.2CHF.sub.2 4-(3-aminopropyl) A-1766 CH.sub.2CHF.sub.2 5-(3-aminopropyl) A-1767 CH.sub.2CHF.sub.2 6-(3-aminopropyl) A-1768 CH.sub.2CHF.sub.2 7-(3-aminopropyl) A-1769 CH.sub.2CHF.sub.2 4-(2-aminopropyl) A-1770 CH.sub.2CHF.sub.2 5-(2-aminopropyl) A-1771 CH.sub.2CHF.sub.2 6-(2-aminopropyl) A-1772 CH.sub.2CHF.sub.2 7-(2-aminopropyl) A-1773 CH.sub.2CHF.sub.2 4-(1-aminopropyl) A-1774 CH.sub.2CHF.sub.2 5-(1-aminopropyl) A-1775 CH.sub.2CHF.sub.2 6-(1-aminopropyl) A-1776 CH.sub.2CHF.sub.2 7-(1-aminopropyl) A-1777 CH.sub.2CHF.sub.2 4-COOH A-1778 CH.sub.2CHF.sub.2 5-COOH A-1779 CH.sub.2CHF.sub.2 6-COOH A-1780 CH.sub.2CHF.sub.2 7-COOH A-1781 CH.sub.2CHF.sub.2 4-COOCH.sub.3 A-1782 CH.sub.2CHF.sub.2 5-COOCH.sub.3 A-1783 CH.sub.2CHF.sub.2 6-COOCH.sub.3 A-1784 CH.sub.2CHF.sub.2 7-COOCH.sub.3 A-1785 CH.sub.2CHF.sub.2 4-COOCH.sub.2CH.sub.3 A-1786 CH.sub.2CHF.sub.2 5-COOCH.sub.2CH.sub.3 A-1787 CH.sub.2CHF.sub.2 6-COOCH.sub.2CH.sub.3 A-1788 CH.sub.2CHF.sub.2 7-COOCH.sub.2CH.sub.3 A-1789 CH.sub.2CHF.sub.2 4-COOCF.sub.3 A-1790 CH.sub.2CHF.sub.2 5-COOCF.sub.3 A-1791 CH.sub.2CHF.sub.2 6-COOCF.sub.3 A-1792 CH.sub.2CHF.sub.2 7-COOCF.sub.3 A-1793 CH.sub.2CHF.sub.2 4-CONH.sub.2 A-1794 CH.sub.2CHF.sub.2 5-CONH.sub.2 A-1795 CH.sub.2CHF.sub.2 6-CONH.sub.2 A-1796 CH.sub.2CHF.sub.2 7-CONH.sub.2 A-1797 CH.sub.2CHF.sub.2 4-CONHCH.sub.3 A-1798 CH.sub.2CHF.sub.2 5-CONHCH.sub.3 A-1799 CH.sub.2CHF.sub.2 6-CONHCH.sub.3 A-1800 CH.sub.2CHF.sub.2 7-CONHCH.sub.3 A-1801 CH.sub.2CHF.sub.2 4-CON(CH.sub.3).sub.2 A-1802 CH.sub.2CHF.sub.2 5-CON(CH.sub.3).sub.2 A-1803 CH.sub.2CHF.sub.2 6-CON(CH.sub.3).sub.2 A-1804 CH.sub.2CHF.sub.2 7-CON(CH.sub.3).sub.2 A-1805 CH.sub.2CHF.sub.2 4-CONHCH.sub.2CH.sub.3 A-1806 CH.sub.2CHF.sub.2 5-CONHCH.sub.2CH.sub.3 A-1807 CH.sub.2CHF.sub.2 6-CONHCH.sub.2CH.sub.3 A-1808 CH.sub.2CHF.sub.2 7-CONHCH.sub.2CH.sub.3 A-1809 CH.sub.2CHF.sub.2 4-CON(CH.sub.2CH.sub.3).sub.2 A-1810 CH.sub.2CHF.sub.2 5-CON(CH.sub.2CH.sub.3).sub.2 A-1811 CH.sub.2CHF.sub.2 6-CON(CH.sub.2CH.sub.3).sub.2 A-1812 CH.sub.2CHF.sub.2 7-CON(CH.sub.2CH.sub.3).sub.2 A-1813 CH.sub.2CHF.sub.2 4-A-1 A-1814 CH.sub.2CHF.sub.2 5-A-1 A-1815 CH.sub.2CHF.sub.2 6-A-1 A-1816 CH.sub.2CHF.sub.2 7-A-1 A-1817 CH.sub.2CHF.sub.2 4-A-2 A-1818 CH.sub.2CHF.sub.2 5-A-2 A-1819 CH.sub.2CHF.sub.2 6-A-2 A-1820 CH.sub.2CHF.sub.2 7-A-2 A-1821 CH.sub.2CHF.sub.2 4-A-3 A-1822 CH.sub.2CHF.sub.2 5-A-3 A-1823 CH.sub.2CHF.sub.2 6-A-3 A-1824 CH.sub.2CHF.sub.2 7-A-3 A-1825 CH.sub.2CHF.sub.2 4-A-4 A-1826 CH.sub.2CHF.sub.2 5-A-4 A-1827 CH.sub.2CHF.sub.2 6-A-4 A-1828 CH.sub.2CHF.sub.2 7-A-4 A-1829 CH.sub.2CHF.sub.2 4-A-5 A-1830 CH.sub.2CHF.sub.2 5-A-5 A-1831 CH.sub.2CHF.sub.2 6-A-5 A-1832 CH.sub.2CHF.sub.2 7-A-5 A-1833 CH.sub.2CHF.sub.2 4-A-6 A-1834 CH.sub.2CHF.sub.2 5-A-6 A-1835 CH.sub.2CHF.sub.2 6-A-6 A-1836 CH.sub.2CHF.sub.2 7-A-6 A-1837 CH.sub.2CHF.sub.2 4-A-7 A-1838 CH.sub.2CHF.sub.2 5-A-7 A-1839 CH.sub.2CHF.sub.2 6-A-7 A-1840 CH.sub.2CHF.sub.2 7-A-7 A-1841 CH.sub.2CHF.sub.2 4-A-8 A-1842 CH.sub.2CHF.sub.2 5-A-8 A-1843 CH.sub.2CHF.sub.2 6-A-8 A-1844 CH.sub.2CHF.sub.2 7-A-8 A-1845 CH.sub.2CHF.sub.2 4-A-9 A-1846 CH.sub.2CHF.sub.2 5-A-9 A-1847 CH.sub.2CHF.sub.2 6-A-9 A-1848 CH.sub.2CHF.sub.2 7-A-9 A-1849 CH.sub.2CHF.sub.2 4-A-10 A-1850 CH.sub.2CHF.sub.2 5-A-10 A-1851 CH.sub.2CHF.sub.2 6-A-10 A-1852 CH.sub.2CHF.sub.2 7-A-10 A-1853 CH.sub.2CHF.sub.2 4-A-11 A-1854 CH.sub.2CHF.sub.2 5-A-11 A-1855 CH.sub.2CHF.sub.2 6-A-11 A-1856 CH.sub.2CHF.sub.2 7-A-11 A-1857 CH.sub.2CHF.sub.2 4-A-12 A-1858 CH.sub.2CHF.sub.2 5-A-12 A-1859 CH.sub.2CHF.sub.2 6-A-12 A-1860 CH.sub.2CHF.sub.2 7-A-12 A-1861 CH.sub.2CHF.sub.2 4-A-13 A-1862 CH.sub.2CHF.sub.2 5-A-13 A-1863 CH.sub.2CHF.sub.2 6-A-13 A-1864 CH.sub.2CHF.sub.2 7-A-13 A-1865 CH.sub.2CHF.sub.2 4-A-14 A-1866 CH.sub.2CHF.sub.2 5-A-14 A-1867 CH.sub.2CHF.sub.2 6-A-14 A-1868 CH.sub.2CHF.sub.2 7-A-14 A-1869 CH.sub.2CHF.sub.2 4-A-15 A-1870 CH.sub.2CHF.sub.2 5-A-15 A-1871 CH.sub.2CHF.sub.2 6-A-15 A-1872 CH.sub.2CHF.sub.2 7-A-15 A-1873 CH.sub.2CHF.sub.2 4-A-16 A-1874 CH.sub.2CHF.sub.2 5-A-16 A-1875 CH.sub.2CHF.sub.2 6-A-16 A-1876 CH.sub.2CHF.sub.2 7-A-16 A-1877 CH.sub.2CHF.sub.2 4-A-17 A-1878 CH.sub.2CHF.sub.2 5-A-17 A-1879 CH.sub.2CHF.sub.2 6-A-17 A-1880 CH.sub.2CHF.sub.2 7-A-17 A-1881 CH.sub.2CHF.sub.2 4-A-18 A-1882 CH.sub.2CHF.sub.2 5-A-18 A-1883 CH.sub.2CHF.sub.2 6-A-18 A-1884 CH.sub.2CHF.sub.2 7-A-18 A-1885 CH.sub.2CHF.sub.2 4-A-19 A-1886 CH.sub.2CHF.sub.2 5-A-19 A-1887 CH.sub.2CHF.sub.2 6-A-19 A-1888 CH.sub.2CHF.sub.2 7-A-19 A-1889 CH.sub.2CHF.sub.2 4-A-20 A-1890 CH.sub.2CHF.sub.2 5-A-20 A-1891 CH.sub.2CHF.sub.2 6-A-20 A-1892 CH.sub.2CHF.sub.2 7-A-20 A-1893 CH.sub.2CHF.sub.2 4-A-21 A-1894 CH.sub.2CHF.sub.2 5-A-21 A-1895 CH.sub.2CHF.sub.2 6-A-21 A-1896 CH.sub.2CHF.sub.2 7-A-21 A-1897 CH.sub.2CHF.sub.2 4-A-22 A-1898 CH.sub.2CHF.sub.2 5-A-22 A-1899 CH.sub.2CHF.sub.2 6-A-22 A-1900 CH.sub.2CHF.sub.2 7-A-22 A-1901 CH.sub.2CHF.sub.2 4-A-23 A-1902 CH.sub.2CHF.sub.2 5-A-23 A-1903 CH.sub.2CHF.sub.2 6-A-23 A-1904 CH.sub.2CHF.sub.2 7-A-23 A-1905 CH.sub.2CHF.sub.2 4-A-24 A-1906 CH.sub.2CHF.sub.2 5-A-24 A-1907 CH.sub.2CHF.sub.2 6-A-24 A-1908 CH.sub.2CHF.sub.2 7-A-24 A-1909 CH.sub.2CHF.sub.2 4-A-25 A-1910 CH.sub.2CHF.sub.2 5-A-25 A-1911 CH.sub.2CHF.sub.2 6-A-25 A-1912 CH.sub.2CHF.sub.2 7-A-25 A-1913 CH.sub.2CHF.sub.2 4-A-26 A-1914 CH.sub.2CHF.sub.2 5-A-26 A-1915 CH.sub.2CHF.sub.2 6-A-26 A-1916 CH.sub.2CHF.sub.2 7-A-26 A-1917 CH.sub.2CHF.sub.2 4-A-27 A-1918 CH.sub.2CHF.sub.2 5-A-27 A-1919 CH.sub.2CHF.sub.2 6-A-27 A-1920 CH.sub.2CHF.sub.2 7-A-27 A-1921 CH.sub.2CHF.sub.2 4-A-28 A-1922 CH.sub.2CHF.sub.2 5-A-28 A-1923 CH.sub.2CHF.sub.2 6-A-28 A-1924 CH.sub.2CHF.sub.2 7-A-28 A-1925 CH.sub.2CHF.sub.2 4-A-29 A-1926 CH.sub.2CHF.sub.2 5-A-29 A-1927 CH.sub.2CHF.sub.2 6-A-29 A-1928 CH.sub.2CHF.sub.2 7-A-29 A-1929 CH.sub.2CHF.sub.2 4-A-30 A-1930 CH.sub.2CHF.sub.2 5-A-30 A-1931 CH.sub.2CHF.sub.2 6-A-30 A-1932 CH.sub.2CHF.sub.2 7-A-30 A-1933 CH.sub.2CHF.sub.2 4-A-31 A-1934 CH.sub.2CHF.sub.2 5-A-31 A-1935 CH.sub.2CHF.sub.2 6-A-31 A-1936 CH.sub.2CHF.sub.2 7-A-31 A-1937 CH.sub.2CHF.sub.2 4-A-32 A-1938 CH.sub.2CHF.sub.2 5-A-32 A-1939 CH.sub.2CHF.sub.2 6-A-32 A-1940 CH.sub.2CHF.sub.2 7-A-32 A-1941 CH.sub.2CHF.sub.2 4-A-33 A-1942 CH.sub.2CHF.sub.2 5-A-33 A-1943 CH.sub.2CHF.sub.2 6-A-33 A-1944 CH.sub.2CHF.sub.2 7-A-33 A-1945 CH.sub.2CHF.sub.2 4-A-34 A-1946 CH.sub.2CHF.sub.2 5-A-34 A-1947 CH.sub.2CHF.sub.2 6-A-34 A-1948 CH.sub.2CHF.sub.2 7-A-34 A-1949 CH.sub.2CHF.sub.2 4-A-35 A-1950 CH.sub.2CHF.sub.2 5-A-35 A-1951 CH.sub.2CHF.sub.2 6-A-35 A-1952 CH.sub.2CHF.sub.2 7-A-35 A-1953 CH.sub.2CHF.sub.2 4-A-36 A-1954 CH.sub.2CHF.sub.2 5-A-36 A-1955 CH.sub.2CHF.sub.2 6-A-36 A-1956 CH.sub.2CHF.sub.2 7-A-36 A-1957 CH.sub.2CHF.sub.2 4-A-37 A-1958 CH.sub.2CHF.sub.2 5-A-37 A-1959 CH.sub.2CHF.sub.2 6-A-37 A-1960 CH.sub.2CHF.sub.2 7-A-37 A-1961 CH.sub.2CHF.sub.2 4-A-38 A-1962 CH.sub.2CHF.sub.2 5-A-38 A-1963 CH.sub.2CHF.sub.2 6-A-38 A-1964 CH.sub.2CHF.sub.2 7-A-38 A-1965 CH.sub.2CHF.sub.2 4-A-39 A-1966 CH.sub.2CHF.sub.2 5-A-39 A-1967 CH.sub.2CHF.sub.2 6-A-39 A-1968 CH.sub.2CHF.sub.2 7-A-39 A-1969 CH.sub.2CHF.sub.2 4-A-40 A-1970 CH.sub.2CHF.sub.2 5-A-40 A-1971 CH.sub.2CHF.sub.2 6-A-40 A-1972 CH.sub.2CHF.sub.2 7-A-40 A-1973 CH.sub.2CHF.sub.2 4-A-41 A-1974 CH.sub.2CHF.sub.2 5-A-41 A-1975 CH.sub.2CHF.sub.2 6-A-41 A-1976 CH.sub.2CHF.sub.2 7-A-41 A-1977 CH.sub.2CHF.sub.2 4-A-42 A-1978 CH.sub.2CHF.sub.2 5-A-42 A-1979 CH.sub.2CHF.sub.2 6-A-42 A-1980 CH.sub.2CHF.sub.2 7-A-42 A-1981 CH.sub.2CHF.sub.2 4-A-43 A-1982 CH.sub.2CHF.sub.2 5-A-43 A-1983 CH.sub.2CHF.sub.2 6-A-43 A-1984 CH.sub.2CHF.sub.2 7-A-43 A-1985 CH.sub.2CHF.sub.2 4-A-44 A-1986 CH.sub.2CHF.sub.2 5-A-44 A-1987 CH.sub.2CHF.sub.2 6-A-44 A-1988 CH.sub.2CHF.sub.2 7-A-44 A-1989 CH.sub.2CHF.sub.2 4-A-45 A-1990 CH.sub.2CHF.sub.2 5-A-45 A-1991 CH.sub.2CHF.sub.2 6-A-45 A-1992 CH.sub.2CHF.sub.2 7-A-45 A-1993 CH.sub.2CHF.sub.2 4-A-46 A-1994 CH.sub.2CHF.sub.2 5-A-46 A-1995 CH.sub.2CHF.sub.2 6-A-46 A-1996 CH.sub.2CHF.sub.2 7-A-46 A-1997 CH.sub.2CHF.sub.2 4-A-47 A-1998 CH.sub.2CHF.sub.2 5-A-47 A-1999 CH.sub.2CHF.sub.2 6-A-47 A-2000 CH.sub.2CHF.sub.2 7-A-47 A-2001 CH.sub.2CHF.sub.2 4-A-48

A-2002 CH.sub.2CHF.sub.2 5-A-48 A-2003 CH.sub.2CHF.sub.2 6-A-48 A-2004 CH.sub.2CHF.sub.2 7-A-48 A-2005 CH.sub.2CHF.sub.2 4-A-49 A-2006 CH.sub.2CHF.sub.2 5-A-49 A-2007 CH.sub.2CHF.sub.2 6-A-49 A-2008 CH.sub.2CHF.sub.2 7-A-49 A-2009 CH.sub.2CHF.sub.2 4-A-50 A-2010 CH.sub.2CHF.sub.2 5-A-50 A-2011 CH.sub.2CHF.sub.2 6-A-50 A-2012 CH.sub.2CHF.sub.2 7-A-50 A-2013 CH.sub.2CHF.sub.2 4-A-51 A-2014 CH.sub.2CHF.sub.2 5-A-51 A-2015 CH.sub.2CHF.sub.2 6-A-51 A-2016 CH.sub.2CHF.sub.2 7-A-51 A-2017 CH.sub.2CHF.sub.2 4-A-52 A-2018 CH.sub.2CHF.sub.2 5-A-52 A-2019 CH.sub.2CHF.sub.2 6-A-52 A-2020 CH.sub.2CHF.sub.2 7-A-52 A-2021 CH.sub.2CHF.sub.2 4-A-53 A-2022 CH.sub.2CHF.sub.2 5-A-53 A-2023 CH.sub.2CHF.sub.2 6-A-53 A-2024 CH.sub.2CHF.sub.2 7-A-53 A-2025 CH.sub.2CHF.sub.2 4-A-54 A-2026 CH.sub.2CHF.sub.2 5-A-54 A-2027 CH.sub.2CHF.sub.2 6-A-54 A-2028 CH.sub.2CHF.sub.2 7-A-54 A-2029 CH.sub.2CHF.sub.2 4-A-55 A-2030 CH.sub.2CHF.sub.2 5-A-55 A-2031 CH.sub.2CHF.sub.2 6-A-55 A-2032 CH.sub.2CHF.sub.2 7-A-55 A-2033 CH.sub.2CHF.sub.2 4-A-56 A-2034 CH.sub.2CHF.sub.2 5-A-56 A-2035 CH.sub.2CHF.sub.2 6-A-56 A-2036 CH.sub.2CHF.sub.2 7-A-56 A-2037 CH.sub.2CHF.sub.2 4-A-57 A-2038 CH.sub.2CHF.sub.2 5-A-57 A-2039 CH.sub.2CHF.sub.2 6-A-57 A-2040 CH.sub.2CHF.sub.2 7-A-57 A-2041 CH.sub.2CHF.sub.2 4-A-58 A-2042 CH.sub.2CHF.sub.2 5-A-58 A-2043 CH.sub.2CHF.sub.2 6-A-58 A-2044 CH.sub.2CHF.sub.2 7-A-58 A-2045 CH.sub.2CHF.sub.2 4-A-59 A-2046 CH.sub.2CHF.sub.2 5-A-59 A-2047 CH.sub.2CHF.sub.2 6-A-59 A-2048 CH.sub.2CHF.sub.2 7-A-59 A-2049 CH.sub.2CHF.sub.2 4-A-60 A-2050 CH.sub.2CHF.sub.2 5-A-60 A-2051 CH.sub.2CHF.sub.2 6-A-60 A-2052 CH.sub.2CHF.sub.2 7-A-60 A-2053 CH.sub.2CHF.sub.2 4-A-61 A-2054 CH.sub.2CHF.sub.2 5-A-61 A-2055 CH.sub.2CHF.sub.2 6-A-61 A-2056 CH.sub.2CHF.sub.2 7-A-61 A-2057 CH.sub.2CHF.sub.2 4-A-62 A-2058 CH.sub.2CHF.sub.2 5-A-62 A-2059 CH.sub.2CHF.sub.2 6-A-62 A-2060 CH.sub.2CHF.sub.2 7-A-62 A-2061 CH.sub.2CHF.sub.2 4-A-63 A-2062 CH.sub.2CHF.sub.2 5-A-63 A-2063 CH.sub.2CHF.sub.2 6-A-63 A-2064 CH.sub.2CHF.sub.2 7-A-63 A-2065 CH.sub.2CHF.sub.2 4-A-64 A-2066 CH.sub.2CHF.sub.2 5-A-64 A-2067 CH.sub.2CHF.sub.2 6-A-64 A-2068 CH.sub.2CHF.sub.2 7-A-64 A-2069 CH.sub.2CHF.sub.2 4-A-65 A-2070 CH.sub.2CHF.sub.2 5-A-65 A-2071 CH.sub.2CHF.sub.2 6-A-65 A-2072 CH.sub.2CHF.sub.2 7-A-65 A-2073 CH.sub.2CHF.sub.2 4-A-66 A-2074 CH.sub.2CHF.sub.2 5-A-66 A-2075 CH.sub.2CHF.sub.2 6-A-66 A-2076 CH.sub.2CHF.sub.2 7-A-66 A-2077 CH.sub.2CHF.sub.2 4-A-67 A-2078 CH.sub.2CHF.sub.2 5-A-67 A-2079 CH.sub.2CHF.sub.2 6-A-67 A-2080 CH.sub.2CHF.sub.2 7-A-67 A-2081 CH.sub.2CHF.sub.2 4-A-68 A-2082 CH.sub.2CHF.sub.2 5-A-68 A-2083 CH.sub.2CHF.sub.2 6-A-68 A-2084 CH.sub.2CHF.sub.2 7-A-68 A-2085 CH.sub.2CHF.sub.2 4-A-69 A-2086 CH.sub.2CHF.sub.2 5-A-69 A-2087 CH.sub.2CHF.sub.2 6-A-69 A-2088 CH.sub.2CHF.sub.2 7-A-69 A-2089 CH.sub.2CHF.sub.2 4-A-70 A-2090 CH.sub.2CHF.sub.2 5-A-70 A-2091 CH.sub.2CHF.sub.2 6-A-70 A-2092 CH.sub.2CHF.sub.2 7-A-70 A-2093 CH.sub.2CHF.sub.2 4-A-71 A-2094 CH.sub.2CHF.sub.2 5-A-71 A-2095 CH.sub.2CHF.sub.2 6-A-71 A-2096 CH.sub.2CHF.sub.2 7-A-71 A-2097 CH.sub.2CHF.sub.2 4-A-72 A-2098 CH.sub.2CHF.sub.2 5-A-72 A-2099 CH.sub.2CHF.sub.2 6-A-72 A-2100 CH.sub.2CHF.sub.2 7-A-72 A-2101 CH.sub.2CHF.sub.2 4-A-73 A-2102 CH.sub.2CHF.sub.2 5-A-73 A-2103 CH.sub.2CHF.sub.2 6-A-73 A-2104 CH.sub.2CHF.sub.2 7-A-73 A-2105 CH.sub.2CHF.sub.2 4-A-74 A-2106 CH.sub.2CHF.sub.2 5-A-74 A-2107 CH.sub.2CHF.sub.2 6-A-74 A-2108 CH.sub.2CHF.sub.2 7-A-74 A-2109 CH.sub.2CHF.sub.2 4-A-75 A-2110 CH.sub.2CHF.sub.2 5-A-75 A-2111 CH.sub.2CHF.sub.2 6-A-75 A-2112 CH.sub.2CHF.sub.2 7-A-75 A-2113 CH.sub.2CHF.sub.2 4-A-76 A-2114 CH.sub.2CHF.sub.2 5-A-76 A-2115 CH.sub.2CHF.sub.2 6-A-76 A-2116 CH.sub.2CHF.sub.2 7-A-76 A-2117 CH.sub.2CHF.sub.2 4-A-77 A-2118 CH.sub.2CHF.sub.2 5-A-77 A-2119 CH.sub.2CHF.sub.2 6-A-77 A-2120 CH.sub.2CHF.sub.2 7-A-77 A-2121 CH.sub.2CHF.sub.2 4-A-78 A-2122 CH.sub.2CHF.sub.2 5-A-78 A-2123 CH.sub.2CHF.sub.2 6-A-78 A-2124 CH.sub.2CHF.sub.2 7-A-78 A-2125 CH.sub.2CHF.sub.2 4-A-79 A-2126 CH.sub.2CHF.sub.2 5-A-79 A-2127 CH.sub.2CHF.sub.2 6-A-79 A-2128 CH.sub.2CHF.sub.2 7-A-79 A-2129 CH.sub.2CHF.sub.2 4-A-80 A-2130 CH.sub.2CHF.sub.2 5-A-80 A-2131 CH.sub.2CHF.sub.2 6-A-80 A-2132 CH.sub.2CHF.sub.2 7-A-80 A-2133 CH.sub.2CHF.sub.2 4-A-81 A-2134 CH.sub.2CHF.sub.2 5-A-81 A-2135 CH.sub.2CHF.sub.2 6-A-81 A-2136 CH.sub.2CHF.sub.2 7-A-81 A-2137 CH.sub.2CHF.sub.2 4-A-82 A-2138 CH.sub.2CHF.sub.2 5-A-82 A-2139 CH.sub.2CHF.sub.2 6-A-82 A-2140 CH.sub.2CHF.sub.2 7-A-82 A-2141 CH.sub.2CHF.sub.2 4-A-83 A-2142 CH.sub.2CHF.sub.2 5-A-83 A-2143 CH.sub.2CHF.sub.2 6-A-83 A-2144 CH.sub.2CHF.sub.2 7-A-83 A-2145 CH.sub.2CHF.sub.2 4-A-84 A-2146 CH.sub.2CHF.sub.2 5-A-84 A-2147 CH.sub.2CHF.sub.2 6-A-84 A-2148 CH.sub.2CHF.sub.2 7-A-84 A-2149 CH.sub.2CHF.sub.2 4-A-85 A-2150 CH.sub.2CHF.sub.2 5-A-85 A-2151 CH.sub.2CHF.sub.2 6-A-85 A-2152 CH.sub.2CHF.sub.2 7-A-85 A-2153 CH.sub.2CHF.sub.2 4-A-86 A-2154 CH.sub.2CHF.sub.2 5-A-86 A-2155 CH.sub.2CHF.sub.2 6-A-86 A-2156 CH.sub.2CHF.sub.2 7-A-86 A-2157 CH.sub.2CHF.sub.2 4-A-87 A-2158 CH.sub.2CHF.sub.2 5-A-87 A-2159 CH.sub.2CHF.sub.2 6-A-87 A-2160 CH.sub.2CHF.sub.2 7-A-87 A-2161 CH.sub.2CHF.sub.2 4-A-88 A-2162 CH.sub.2CHF.sub.2 5-A-88 A-2163 CH.sub.2CHF.sub.2 6-A-88 A-2164 CH.sub.2CHF.sub.2 7-A-88 A-2165 CH.sub.2CHF.sub.2 4-A-89 A-2166 CH.sub.2CHF.sub.2 5-A-89 A-2167 CH.sub.2CHF.sub.2 6-A-89 A-2168 CH.sub.2CHF.sub.2 7-A-89 A-2169 CH.sub.2CHF.sub.2 4-A-90 A-2170 CH.sub.2CHF.sub.2 5-A-90 A-2171 CH.sub.2CHF.sub.2 6-A-90 A-2172 CH.sub.2CHF.sub.2 7-A-90 A-2173 CH.sub.2CHF.sub.2 4-A-91 A-2174 CH.sub.2CHF.sub.2 5-A-91 A-2175 CH.sub.2CHF.sub.2 6-A-91 A-2176 CH.sub.2CHF.sub.2 7-A-91 A-2177 CH.sub.2CHF.sub.2 4-A-92 A-2178 CH.sub.2CHF.sub.2 5-A-92 A-2179 CH.sub.2CHF.sub.2 6-A-92 A-2180 CH.sub.2CHF.sub.2 7-A-92 A-2181 CH.sub.2CHF.sub.2 4-A-93 A-2182 CH.sub.2CHF.sub.2 5-A-93 A-2183 CH.sub.2CHF.sub.2 6-A-93 A-2184 CH.sub.2CHF.sub.2 7-A-93 A-2185 CH.sub.2CHF.sub.2 4-A-94 A-2186 CH.sub.2CHF.sub.2 5-A-94 A-2187 CH.sub.2CHF.sub.2 6-A-94 A-2188 CH.sub.2CHF.sub.2 7-A-94 A-2189 CH.sub.2CHF.sub.2 4-A-95 A-2190 CH.sub.2CHF.sub.2 5-A-95 A-2191 CH.sub.2CHF.sub.2 6-A-95 A-2192 CH.sub.2CHF.sub.2 7-A-95 A-2193 CH.sub.2CHF.sub.2 4-A-96 A-2194 CH.sub.2CHF.sub.2 5-A-96 A-2195 CH.sub.2CHF.sub.2 6-A-96 A-2196 CH.sub.2CHF.sub.2 7-A-96 A-2197 CH.sub.2CHF.sub.2 4-A-97 A-2198 CH.sub.2CHF.sub.2 5-A-97 A-2199 CH.sub.2CHF.sub.2 6-A-97 A-2200 CH.sub.2CHF.sub.2 7-A-97 A-2201 CH.sub.2CHF.sub.2 4-A-98 A-2202 CH.sub.2CHF.sub.2 5-A-98 A-2203 CH.sub.2CHF.sub.2 6-A-98 A-2204 CH.sub.2CHF.sub.2 7-A-98 A-2205 CH.sub.2CHF.sub.2 4-A-99 A-2206 CH.sub.2CHF.sub.2 5-A-99 A-2207 CH.sub.2CHF.sub.2 6-A-99 A-2208 CH.sub.2CHF.sub.2 7-A-99 A-2209 CH.sub.2CHF.sub.2 4-A-100 A-2210 CH.sub.2CHF.sub.2 5-A-100 A-2211 CH.sub.2CHF.sub.2 6-A-100 A-2212 CH.sub.2CHF.sub.2 7-A-100 A-2213 CH.sub.2CHF.sub.2 4-A-101 A-2214 CH.sub.2CHF.sub.2 5-A-101 A-2215 CH.sub.2CHF.sub.2 6-A-101 A-2216 CH.sub.2CHF.sub.2 7-A-101 A-2217 CH.sub.2CHF.sub.2 4-A-102 A-2218 CH.sub.2CHF.sub.2 5-A-102 A-2219 CH.sub.2CHF.sub.2 6-A-102 A-2220 CH.sub.2CHF.sub.2 7-A-102 A-2221 CH.sub.2CHF.sub.2 4-A-103 A-2222 CH.sub.2CHF.sub.2 5-A-103 A-2223 CH.sub.2CHF.sub.2 6-A-103 A-2224 CH.sub.2CHF.sub.2 7-A-103 A-2225 CH.sub.2CHF.sub.2 4-A-104 A-2226 CH.sub.2CHF.sub.2 5-A-104 A-2227 CH.sub.2CHF.sub.2 6-A-104 A-2228 CH.sub.2CHF.sub.2 7-A-104 A-2229 CH.sub.2CHF.sub.2 4-A-104 A-2230 CH.sub.2CHF.sub.2 5-A-104 A-2231 CH.sub.2CHF.sub.2 6-A-104 A-2232 CH.sub.2CHF.sub.2 7-A-104 A-2233 CH.sub.2CHF.sub.2 4-A-105 A-2234 CH.sub.2CHF.sub.2 5-A-105 A-2235 CH.sub.2CHF.sub.2 6-A-105 A-2236 CH.sub.2CHF.sub.2 7-A-105 A-2237 CH.sub.2CHF.sub.2 4-A-106 A-2238 CH.sub.2CHF.sub.2 5-A-106 A-2239 CH.sub.2CHF.sub.2 6-A-106 A-2240 CH.sub.2CHF.sub.2 7-A-106 A-2241 CH.sub.2CHF.sub.2 4-A-107 A-2242 CH.sub.2CHF.sub.2 5-A-107 A-2243 CH.sub.2CHF.sub.2 6-A-107 A-2244 CH.sub.2CHF.sub.2 7-A-107 A-2245 CH.sub.2CHF.sub.2 4-A-108 A-2246 CH.sub.2CHF.sub.2 5-A-108 A-2247 CH.sub.2CHF.sub.2 6-A-108 A-2248 CH.sub.2CHF.sub.2 7-A-108 A-2249 CH.sub.2CHF.sub.2 4-A-109 A-2250 CH.sub.2CHF.sub.2 5-A-109 A-2251 CH.sub.2CHF.sub.2 6-A-109 A-2252 CH.sub.2CHF.sub.2 7-A-109

A-2253 CH.sub.2CHF.sub.2 4-A-110 A-2254 CH.sub.2CHF.sub.2 5-A-110 A-2255 CH.sub.2CHF.sub.2 6-A-110 A-2256 CH.sub.2CHF.sub.2 7-A-110 A-2257 CH.sub.2CHF.sub.2 4-A-111 A-2258 CH.sub.2CHF.sub.2 5-A-111 A-2259 CH.sub.2CHF.sub.2 6-A-111 A-2260 CH.sub.2CHF.sub.2 7-A-111 A-2261 CH.sub.3 H A-2262 CH.sub.3 4-Cl A-2263 CH.sub.3 5-Cl A-2264 CH.sub.3 6-Cl A-2265 CH.sub.3 7-Cl A-2266 CH.sub.3 4-Br A-2267 CH.sub.3 5-Br A-2268 CH.sub.3 6-Br A-2269 CH.sub.3 7-Br A-2270 CH.sub.3 4-CN A-2271 CH.sub.3 5-CN A-2272 CH.sub.3 6-CN A-2273 CH.sub.3 7-CN A-2274 CH.sub.3 4-OH A-2275 CH.sub.3 5-OH A-2276 CH.sub.3 6-OH A-2277 CH.sub.3 7-OH A-2278 CH.sub.3 4-methyl A-2279 CH.sub.3 5-methyl A-2280 CH.sub.3 6-methyl A-2281 CH.sub.3 7-methyl A-2282 CH.sub.3 4-ethyl A-2283 CH.sub.3 5-ethyl A-2284 CH.sub.3 6-ethyl A-2285 CH.sub.3 7-ethyl A-2286 CH.sub.3 4-propyl A-2287 CH.sub.3 5-propyl A-2288 CH.sub.3 6-propyl A-2289 CH.sub.3 7-propyl A-2290 CH.sub.3 4-isopropyl A-2291 CH.sub.3 5-isopropyl A-2292 CH.sub.3 6-isopropyl A-2293 CH.sub.3 7-isopropyl A-2294 CH.sub.3 4-hydroxymethyl A-2295 CH.sub.3 5-hydroxymethyl A-2296 CH.sub.3 6-hydroxymethyl A-2297 CH.sub.3 7-hydroxymethyl A-2298 CH.sub.3 4-(2-hydroxyethyl) A-2299 CH.sub.3 5-(2-hydroxyethyl) A-2300 CH.sub.3 6-(2-hydroxyethyl) A-2301 CH.sub.3 7-(2-hydroxyethyl) A-2302 CH.sub.3 4-(1-hydroxyethyl) A-2303 CH.sub.3 5-(1-hydroxyethyl) A-2304 CH.sub.3 6-(1-hydroxyethyl) A-2305 CH.sub.3 7-(1-hydroxyethyl) A-2306 CH.sub.3 4-(3-hydroxypropyl) A-2307 CH.sub.3 5-(3-hydroxypropyl) A-2308 CH.sub.3 6-(3-hydroxypropyl) A-2309 CH.sub.3 7-(3-hydroxypropyl) A-2310 CH.sub.3 4-(2-hydroxypropyl) A-2311 CH.sub.3 5-(2-hydroxypropyl) A-2312 CH.sub.3 6-(2-hydroxypropyl) A-2313 CH.sub.3 7-(2-hydroxypropyl) A-2314 CH.sub.3 4-(1-hydroxypropyl) A-2315 CH.sub.3 5-(1-hydroxypropyl) A-2316 CH.sub.3 6-(1-hydroxypropyl) A-2317 CH.sub.3 7-(1-hydroxypropyl) A-2318 CH.sub.3 4-aminomethyl A-2319 CH.sub.3 5-aminomethyl A-2320 CH.sub.3 6-aminomethyl A-2321 CH.sub.3 7-aminomethyl A-2322 CH.sub.3 4-(2-aminoethyl) A-2323 CH.sub.3 5-(2-aminoethyl) A-2324 CH.sub.3 6-(2-aminoethyl) A-2325 CH.sub.3 7-(2-aminoethyl) A-2326 CH.sub.3 4-(1-aminoethyl) A-2327 CH.sub.3 5-(1-aminoethyl) A-2328 CH.sub.3 6-(1-aminoethyl) A-2329 CH.sub.3 7-(1-aminoethyl) A-2330 CH.sub.3 4-(3-aminopropyl) A-2331 CH.sub.3 5-(3-aminopropyl) A-2332 CH.sub.3 6-(3-aminopropyl) A-2333 CH.sub.3 7-(3-aminopropyl) A-2334 CH.sub.3 4-(2-aminopropyl) A-2335 CH.sub.3 5-(2-aminopropyl) A-2336 CH.sub.3 6-(2-aminopropyl) A-2337 CH.sub.3 7-(2-aminopropyl) A-2338 CH.sub.3 4-(1-aminopropyl) A-2339 CH.sub.3 5-(1-aminopropyl) A-2340 CH.sub.3 6-(1-aminopropyl) A-2341 CH.sub.3 7-(1-aminopropyl) A-2342 CH.sub.3 4-COOH A-2343 CH.sub.3 5-COOH A-2344 CH.sub.3 6-COOH A-2345 CH.sub.3 7-COOH A-2346 CH.sub.3 4-COOCH.sub.3 A-2347 CH.sub.3 5-COOCH.sub.3 A-2348 CH.sub.3 6-COOCH.sub.3 A-2349 CH.sub.3 7-COOCH.sub.3 A-2350 CH.sub.3 4-COOCH.sub.2CH.sub.3 A-2351 CH.sub.3 5-COOCH.sub.2CH.sub.3 A-2352 CH.sub.3 6-COOCH.sub.2CH.sub.3 A-2353 CH.sub.3 7-COOCH.sub.2CH.sub.3 A-2354 CH.sub.3 4-COOCF.sub.3 A-2355 CH.sub.3 5-COOCF.sub.3 A-2356 CH.sub.3 6-COOCF.sub.3 A-2357 CH.sub.3 7-COOCF.sub.3 A-2358 CH.sub.3 4-CONH.sub.2 A-2359 CH.sub.3 5-CONH.sub.2 A-2360 CH.sub.3 6-CONH.sub.2 A-2361 CH.sub.3 7-CONH.sub.2 A-2362 CH.sub.3 4-CONHCH.sub.3 A-2363 CH.sub.3 5-CONHCH.sub.3 A-2364 CH.sub.3 6-CONHCH.sub.3 A-2365 CH.sub.3 7-CONHCH.sub.3 A-2366 CH.sub.3 4-CON(CH.sub.3).sub.2 A-2367 CH.sub.3 5-CON(CH.sub.3).sub.2 A-2368 CH.sub.3 6-CON(CH.sub.3).sub.2 A-2369 CH.sub.3 7-CON(CH.sub.3).sub.2 A-2370 CH.sub.3 4-CONHCH.sub.2CH.sub.3 A-2371 CH.sub.3 5-CONHCH.sub.2CH.sub.3 A-2372 CH.sub.3 6-CONHCH.sub.2CH.sub.3 A-2373 CH.sub.3 7-CONHCH.sub.2CH.sub.3 A-2374 CH.sub.3 4-CON(CH.sub.2CH.sub.3).sub.2 A-2375 CH.sub.3 5-CON(CH.sub.2CH.sub.3).sub.2 A-2376 CH.sub.3 6-CON(CH.sub.2CH.sub.3).sub.2 A-2377 CH.sub.3 7-CON(CH.sub.2CH.sub.3).sub.2 A-2378 CH.sub.3 4-A-1 A-2379 CH.sub.3 5-A-1 A-2380 CH.sub.3 6-A-1 A-2381 CH.sub.3 7-A-1 A-2382 CH.sub.3 4-A-2 A-2383 CH.sub.3 5-A-2 A-2384 CH.sub.3 6-A-2 A-2385 CH.sub.3 7-A-2 A-2386 CH.sub.3 4-A-3 A-2387 CH.sub.3 5-A-3 A-2388 CH.sub.3 6-A-3 A-2389 CH.sub.3 7-A-3 A-2390 CH.sub.3 4-A-4 A-2391 CH.sub.3 5-A-4 A-2392 CH.sub.3 6-A-4 A-2393 CH.sub.3 7-A-4 A-2394 CH.sub.3 4-A-5 A-2395 CH.sub.3 5-A-5 A-2396 CH.sub.3 6-A-5 A-2397 CH.sub.3 7-A-5 A-2398 CH.sub.3 4-A-6 A-2399 CH.sub.3 5-A-6 A-2400 CH.sub.3 6-A-6 A-2401 CH.sub.3 7-A-6 A-2402 CH.sub.3 4-A-7 A-2403 CH.sub.3 5-A-7 A-2404 CH.sub.3 6-A-7 A-2405 CH.sub.3 7-A-7 A-2406 CH.sub.3 4-A-8 A-2407 CH.sub.3 5-A-8 A-2408 CH.sub.3 6-A-8 A-2409 CH.sub.3 7-A-8 A-2410 CH.sub.3 4-A-9 A-2411 CH.sub.3 5-A-9 A-2412 CH.sub.3 6-A-9 A-2413 CH.sub.3 7-A-9 A-2414 CH.sub.3 4-A-10 A-2415 CH.sub.3 5-A-10 A-2416 CH.sub.3 6-A-10 A-2417 CH.sub.3 7-A-10 A-2418 CH.sub.3 4-A-11 A-2419 CH.sub.3 5-A-11 A-2420 CH.sub.3 6-A-11 A-2421 CH.sub.3 7-A-11 A-2422 CH.sub.3 4-A-12 A-2423 CH.sub.3 5-A-12 A-2424 CH.sub.3 6-A-12 A-2425 CH.sub.3 7-A-12 A-2426 CH.sub.3 4-A-13 A-2427 CH.sub.3 5-A-13 A-2428 CH.sub.3 6-A-13 A-2429 CH.sub.3 7-A-13 A-2430 CH.sub.3 4-A-14 A-2431 CH.sub.3 5-A-14 A-2432 CH.sub.3 6-A-14 A-2433 CH.sub.3 7-A-14 A-2434 CH.sub.3 4-A-15 A-2435 CH.sub.3 5-A-15 A-2436 CH.sub.3 6-A-15 A-2437 CH.sub.3 7-A-15 A-2438 CH.sub.3 4-A-16 A-2439 CH.sub.3 5-A-16 A-2440 CH.sub.3 6-A-16 A-2441 CH.sub.3 7-A-16 A-2442 CH.sub.3 4-A-17 A-2443 CH.sub.3 5-A-17 A-2444 CH.sub.3 6-A-17 A-2445 CH.sub.3 7-A-17 A-2446 CH.sub.3 4-A-18 A-2447 CH.sub.3 5-A-18 A-2448 CH.sub.3 6-A-18 A-2449 CH.sub.3 7-A-18 A-2450 CH.sub.3 4-A-19 A-2451 CH.sub.3 5-A-19 A-2452 CH.sub.3 6-A-19 A-2453 CH.sub.3 7-A-19 A-2454 CH.sub.3 4-A-20 A-2455 CH.sub.3 5-A-20 A-2456 CH.sub.3 6-A-20 A-2457 CH.sub.3 7-A-20 A-2458 CH.sub.3 4-A-21 A-2459 CH.sub.3 5-A-21 A-2460 CH.sub.3 6-A-21 A-2461 CH.sub.3 7-A-21 A-2462 CH.sub.3 4-A-22 A-2463 CH.sub.3 5-A-22 A-2464 CH.sub.3 6-A-22 A-2465 CH.sub.3 7-A-22 A-2466 CH.sub.3 4-A-23 A-2467 CH.sub.3 5-A-23 A-2468 CH.sub.3 6-A-23 A-2469 CH.sub.3 7-A-23 A-2470 CH.sub.3 4-A-24 A-2471 CH.sub.3 5-A-24 A-2472 CH.sub.3 6-A-24 A-2473 CH.sub.3 7-A-24 A-2474 CH.sub.3 4-A-25 A-2475 CH.sub.3 5-A-25 A-2476 CH.sub.3 6-A-25 A-2477 CH.sub.3 7-A-25 A-2478 CH.sub.3 4-A-26 A-2479 CH.sub.3 5-A-26 A-2480 CH.sub.3 6-A-26 A-2481 CH.sub.3 7-A-26 A-2482 CH.sub.3 4-A-27 A-2483 CH.sub.3 5-A-27 A-2484 CH.sub.3 6-A-27 A-2485 CH.sub.3 7-A-27 A-2486 CH.sub.3 4-A-28 A-2487 CH.sub.3 5-A-28 A-2488 CH.sub.3 6-A-28 A-2489 CH.sub.3 7-A-28 A-2490 CH.sub.3 4-A-29 A-2491 CH.sub.3 5-A-29 A-2492 CH.sub.3 6-A-29 A-2493 CH.sub.3 7-A-29 A-2494 CH.sub.3 4-A-30 A-2495 CH.sub.3 5-A-30 A-2496 CH.sub.3 6-A-30 A-2497 CH.sub.3 7-A-30 A-2498 CH.sub.3 4-A-31 A-2499 CH.sub.3 5-A-31 A-2500 CH.sub.3 6-A-31 A-2501 CH.sub.3 7-A-31 A-2502 CH.sub.3 4-A-32 A-2503 CH.sub.3 5-A-32

A-2504 CH.sub.3 6-A-32 A-2505 CH.sub.3 7-A-32 A-2506 CH.sub.3 4-A-33 A-2507 CH.sub.3 5-A-33 A-2508 CH.sub.3 6-A-33 A-2509 CH.sub.3 7-A-33 A-2510 CH.sub.3 4-A-34 A-2511 CH.sub.3 5-A-34 A-2512 CH.sub.3 6-A-34 A-2513 CH.sub.3 7-A-34 A-2514 CH.sub.3 4-A-35 A-2515 CH.sub.3 5-A-35 A-2516 CH.sub.3 6-A-35 A-2517 CH.sub.3 7-A-35 A-2518 CH.sub.3 4-A-36 A-2519 CH.sub.3 5-A-36 A-2520 CH.sub.3 6-A-36 A-2521 CH.sub.3 7-A-36 A-2522 CH.sub.3 4-A-37 A-2523 CH.sub.3 5-A-37 A-2524 CH.sub.3 6-A-37 A-2525 CH.sub.3 7-A-37 A-2526 CH.sub.3 4-A-38 A-2527 CH.sub.3 5-A-38 A-2528 CH.sub.3 6-A-38 A-2529 CH.sub.3 7-A-38 A-2530 CH.sub.3 4-A-39 A-2531 CH.sub.3 5-A-39 A-2532 CH.sub.3 6-A-39 A-2533 CH.sub.3 7-A-39 A-2534 CH.sub.3 4-A-40 A-2535 CH.sub.3 5-A-40 A-2536 CH.sub.3 6-A-40 A-2537 CH.sub.3 7-A-40 A-2538 CH.sub.3 4-A-41 A-2539 CH.sub.3 5-A-41 A-2540 CH.sub.3 6-A-41 A-2541 CH.sub.3 7-A-41 A-2542 CH.sub.3 4-A-42 A-2543 CH.sub.3 5-A-42 A-2544 CH.sub.3 6-A-42 A-2545 CH.sub.3 7-A-42 A-2546 CH.sub.3 4-A-43 A-2547 CH.sub.3 5-A-43 A-2548 CH.sub.3 6-A-43 A-2549 CH.sub.3 7-A-43 A-2550 CH.sub.3 4-A-44 A-2551 CH.sub.3 5-A-44 A-2552 CH.sub.3 6-A-44 A-2553 CH.sub.3 7-A-44 A-2554 CH.sub.3 4-A-45 A-2555 CH.sub.3 5-A-45 A-2556 CH.sub.3 6-A-45 A-2557 CH.sub.3 7-A-45 A-2558 CH.sub.3 4-A-46 A-2559 CH.sub.3 5-A-46 A-2560 CH.sub.3 6-A-46 A-2561 CH.sub.3 7-A-46 A-2562 CH.sub.3 4-A-47 A-2563 CH.sub.3 5-A-47 A-2564 CH.sub.3 6-A-47 A-2565 CH.sub.3 7-A-47 A-2566 CH.sub.3 4-A-48 A-2567 CH.sub.3 5-A-48 A-2568 CH.sub.3 6-A-48 A-2569 CH.sub.3 7-A-48 A-2570 CH.sub.3 4-A-49 A-2571 CH.sub.3 5-A-49 A-2572 CH.sub.3 6-A-49 A-2573 CH.sub.3 7-A-49 A-2574 CH.sub.3 4-A-50 A-2575 CH.sub.3 5-A-50 A-2576 CH.sub.3 6-A-50 A-2577 CH.sub.3 7-A-50 A-2578 CH.sub.3 4-A-51 A-2579 CH.sub.3 5-A-51 A-2580 CH.sub.3 6-A-51 A-2581 CH.sub.3 7-A-51 A-2582 CH.sub.3 4-A-52 A-2583 CH.sub.3 5-A-52 A-2584 CH.sub.3 6-A-52 A-2585 CH.sub.3 7-A-52 A-2586 CH.sub.3 4-A-53 A-2587 CH.sub.3 5-A-53 A-2588 CH.sub.3 6-A-53 A-2589 CH.sub.3 7-A-53 A-2590 CH.sub.3 4-A-54 A-2591 CH.sub.3 5-A-54 A-2592 CH.sub.3 6-A-54 A-2593 CH.sub.3 7-A-54 A-2594 CH.sub.3 4-A-55 A-2595 CH.sub.3 5-A-55 A-2596 CH.sub.3 6-A-55 A-2597 CH.sub.3 7-A-55 A-2598 CH.sub.3 4-A-56 A-2599 CH.sub.3 5-A-56 A-2600 CH.sub.3 6-A-56 A-2601 CH.sub.3 7-A-56 A-2602 CH.sub.3 4-A-57 A-2603 CH.sub.3 5-A-57 A-2604 CH.sub.3 6-A-57 A-2605 CH.sub.3 7-A-57 A-2606 CH.sub.3 4-A-58 A-2607 CH.sub.3 5-A-58 A-2608 CH.sub.3 6-A-58 A-2609 CH.sub.3 7-A-58 A-2610 CH.sub.3 4-A-59 A-2611 CH.sub.3 5-A-59 A-2612 CH.sub.3 6-A-59 A-2613 CH.sub.3 7-A-59 A-2614 CH.sub.3 4-A-60 A-2615 CH.sub.3 5-A-60 A-2616 CH.sub.3 6-A-60 A-2617 CH.sub.3 7-A-60 A-2618 CH.sub.3 4-A-61 A-2619 CH.sub.3 5-A-61 A-2620 CH.sub.3 6-A-61 A-2621 CH.sub.3 7-A-61 A-2622 CH.sub.3 4-A-62 A-2623 CH.sub.3 5-A-62 A-2624 CH.sub.3 6-A-62 A-2625 CH.sub.3 7-A-62 A-2626 CH.sub.3 4-A-63 A-2627 CH.sub.3 5-A-63 A-2628 CH.sub.3 6-A-63 A-2629 CH.sub.3 7-A-63 A-2630 CH.sub.3 4-A-64 A-2631 CH.sub.3 5-A-64 A-2632 CH.sub.3 6-A-64 A-2633 CH.sub.3 7-A-64 A-2634 CH.sub.3 4-A-65 A-2635 CH.sub.3 5-A-65 A-2636 CH.sub.3 6-A-65 A-2637 CH.sub.3 7-A-65 A-2638 CH.sub.3 4-A-66 A-2639 CH.sub.3 5-A-66 A-2640 CH.sub.3 6-A-66 A-2641 CH.sub.3 7-A-66 A-2642 CH.sub.3 4-A-67 A-2643 CH.sub.3 5-A-67 A-2644 CH.sub.3 6-A-67 A-2645 CH.sub.3 7-A-67 A-2646 CH.sub.3 4-A-68 A-2647 CH.sub.3 5-A-68 A-2648 CH.sub.3 6-A-68 A-2649 CH.sub.3 7-A-68 A-2650 CH.sub.3 4-A-69 A-2651 CH.sub.3 5-A-69 A-2652 CH.sub.3 6-A-69 A-2653 CH.sub.3 7-A-69 A-2654 CH.sub.3 4-A-70 A-2655 CH.sub.3 5-A-70 A-2656 CH.sub.3 6-A-70 A-2657 CH.sub.3 7-A-70 A-2658 CH.sub.3 4-A-71 A-2659 CH.sub.3 5-A-71 A-2660 CH.sub.3 6-A-71 A-2661 CH.sub.3 7-A-71 A-2662 CH.sub.3 4-A-72 A-2663 CH.sub.3 5-A-72 A-2664 CH.sub.3 6-A-72 A-2665 CH.sub.3 7-A-72 A-2666 CH.sub.3 4-A-73 A-2667 CH.sub.3 5-A-73 A-2668 CH.sub.3 6-A-73 A-2669 CH.sub.3 7-A-73 A-2670 CH.sub.3 4-A-74 A-2671 CH.sub.3 5-A-74 A-2672 CH.sub.3 6-A-74 A-2673 CH.sub.3 7-A-74 A-2674 CH.sub.3 4-A-75 A-2675 CH.sub.3 5-A-75 A-2676 CH.sub.3 6-A-75 A-2677 CH.sub.3 7-A-75 A-2678 CH.sub.3 4-A-76 A-2679 CH.sub.3 5-A-76 A-2680 CH.sub.3 6-A-76 A-2681 CH.sub.3 7-A-76 A-2682 CH.sub.3 4-A-77 A-2683 CH.sub.3 5-A-77 A-2684 CH.sub.3 6-A-77 A-2685 CH.sub.3 7-A-77 A-2686 CH.sub.3 4-A-78 A-2687 CH.sub.3 5-A-78 A-2688 CH.sub.3 6-A-78 A-2689 CH.sub.3 7-A-78 A-2690 CH.sub.3 4-A-79 A-2691 CH.sub.3 5-A-79 A-2692 CH.sub.3 6-A-79 A-2693 CH.sub.3 7-A-79 A-2694 CH.sub.3 4-A-80 A-2695 CH.sub.3 5-A-80 A-2696 CH.sub.3 6-A-80 A-2697 CH.sub.3 7-A-80 A-2698 CH.sub.3 4-A-81 A-2699 CH.sub.3 5-A-81 A-2700 CH.sub.3 6-A-81 A-2701 CH.sub.3 7-A-81 A-2702 CH.sub.3 4-A-82 A-2703 CH.sub.3 5-A-82 A-2704 CH.sub.3 6-A-82 A-2705 CH.sub.3 7-A-82 A-2706 CH.sub.3 4-A-83 A-2707 CH.sub.3 5-A-83 A-2708 CH.sub.3 6-A-83 A-2709 CH.sub.3 7-A-83 A-2710 CH.sub.3 4-A-84 A-2711 CH.sub.3 5-A-84 A-2712 CH.sub.3 6-A-84 A-2713 CH.sub.3 7-A-84 A-2714 CH.sub.3 4-A-85 A-2715 CH.sub.3 5-A-85 A-2716 CH.sub.3 6-A-85 A-2717 CH.sub.3 7-A-85 A-2718 CH.sub.3 4-A-86 A-2719 CH.sub.3 5-A-86 A-2720 CH.sub.3 6-A-86 A-2721 CH.sub.3 7-A-86 A-2722 CH.sub.3 4-A-87 A-2723 CH.sub.3 5-A-87 A-2724 CH.sub.3 6-A-87 A-2725 CH.sub.3 7-A-87 A-2726 CH.sub.3 4-A-88 A-2727 CH.sub.3 5-A-88 A-2728 CH.sub.3 6-A-88 A-2729 CH.sub.3 7-A-88 A-2730 CH.sub.3 4-A-89 A-2731 CH.sub.3 5-A-89 A-2732 CH.sub.3 6-A-89 A-2733 CH.sub.3 7-A-89 A-2734 CH.sub.3 4-A-90 A-2735 CH.sub.3 5-A-90 A-2736 CH.sub.3 6-A-90 A-2737 CH.sub.3 7-A-90 A-2738 CH.sub.3 4-A-91 A-2739 CH.sub.3 5-A-91 A-2740 CH.sub.3 6-A-91 A-2741 CH.sub.3 7-A-91 A-2742 CH.sub.3 4-A-92 A-2743 CH.sub.3 5-A-92 A-2744 CH.sub.3 6-A-92 A-2745 CH.sub.3 7-A-92 A-2746 CH.sub.3 4-A-93 A-2747 CH.sub.3 5-A-93 A-2748 CH.sub.3 6-A-93 A-2749 CH.sub.3 7-A-93 A-2750 CH.sub.3 4-A-94 A-2751 CH.sub.3 5-A-94 A-2752 CH.sub.3 6-A-94 A-2753 CH.sub.3 7-A-94 A-2754 CH.sub.3 4-A-95

A-2755 CH.sub.3 5-A-95 A-2756 CH.sub.3 6-A-95 A-2757 CH.sub.3 7-A-95 A-2758 CH.sub.3 4-A-96 A-2759 CH.sub.3 5-A-96 A-2760 CH.sub.3 6-A-96 A-2761 CH.sub.3 7-A-96 A-2762 CH.sub.3 4-A-97 A-2763 CH.sub.3 5-A-97 A-2764 CH.sub.3 6-A-97 A-2765 CH.sub.3 7-A-97 A-2766 CH.sub.3 4-A-98 A-2767 CH.sub.3 5-A-98 A-2768 CH.sub.3 6-A-98 A-2769 CH.sub.3 7-A-98 A-2770 CH.sub.3 4-A-99 A-2771 CH.sub.3 5-A-99 A-2772 CH.sub.3 6-A-99 A-2773 CH.sub.3 7-A-99 A-2774 CH.sub.3 4-A-100 A-2775 CH.sub.3 5-A-100 A-2776 CH.sub.3 6-A-100 A-2777 CH.sub.3 7-A-100 A-2778 CH.sub.3 4-A-101 A-2779 CH.sub.3 5-A-101 A-2780 CH.sub.3 6-A-101 A-2781 CH.sub.3 7-A-101 A-2782 CH.sub.3 4-A-102 A-2783 CH.sub.3 5-A-102 A-2784 CH.sub.3 6-A-102 A-2785 CH.sub.3 7-A-102 A-2786 CH.sub.3 4-A-103 A-2787 CH.sub.3 5-A-103 A-2788 CH.sub.3 6-A-103 A-2789 CH.sub.3 7-A-103 A-2790 CH.sub.3 4-A-104 A-2791 CH.sub.3 5-A-104 A-2792 CH.sub.3 6-A-104 A-2793 CH.sub.3 7-A-104 A-2794 CH.sub.3 4-A-104 A-2795 CH.sub.3 5-A-104 A-2796 CH.sub.3 6-A-104 A-2797 CH.sub.3 7-A-104 A-2798 CH.sub.3 4-A-105 A-2799 CH.sub.3 5-A-105 A-2800 CH.sub.3 6-A-105 A-2801 CH.sub.3 7-A-105 A-2802 CH.sub.3 4-A-106 A-2803 CH.sub.3 5-A-106 A-2804 CH.sub.3 6-A-106 A-2805 CH.sub.3 7-A-106 A-2806 CH.sub.3 4-A-107 A-2807 CH.sub.3 5-A-107 A-2808 CH.sub.3 6-A-107 A-2809 CH.sub.3 7-A-107 A-2810 CH.sub.3 4-A-108 A-2811 CH.sub.3 5-A-108 A-2812 CH.sub.3 6-A-108 A-2813 CH.sub.3 7-A-108 A-2814 CH.sub.3 4-A-109 A-2815 CH.sub.3 5-A-109 A-2816 CH.sub.3 6-A-109 A-2817 CH.sub.3 7-A-109 A-2818 CH.sub.3 4-A-110 A-2819 CH.sub.3 5-A-110 A-2820 CH.sub.3 6-A-110 A-2821 CH.sub.3 7-A-110 A-2822 CH.sub.3 4-A-111 A-2823 CH.sub.3 5-A-111 A-2824 CH.sub.3 6-A-111 A-2825 CH.sub.3 7-A-111 A-2826 OH H A-2827 OH 4-Cl A-2828 OH 5-Cl A-2829 OH 6-Cl A-2830 OH 7-Cl A-2831 OH 4-Br A-2832 OH 5-Br A-2833 OH 6-Br A-2834 OH 7-Br A-2835 OH 4-CN A-2836 OH 5-CN A-2837 OH 6-CN A-2838 OH 7-CN A-2839 OH 4-OH A-2840 OH 5-OH A-2841 OH 6-OH A-2842 OH 7-OH A-2843 OH 4-methyl A-2844 OH 5-methyl A-2845 OH 6-methyl A-2846 OH 7-methyl A-2847 OH 4-ethyl A-2848 OH 5-ethyl A-2849 OH 6-ethyl A-2850 OH 7-ethyl A-2851 OH 4-propyl A-2852 OH 5-propyl A-2853 OH 6-propyl A-2854 OH 7-propyl A-2855 OH 4-isopropyl A-2856 OH 5-isopropyl A-2857 OH 6-isopropyl A-2858 OH 7-isopropyl A-2859 OH 4-hydroxymethyl A-2860 OH 5-hydroxymethyl A-2861 OH 6-hydroxymethyl A-2862 OH 7-hydroxymethyl A-2863 OH 4-(2-hydroxyethyl) A-2864 OH 5-(2-hydroxyethyl) A-2865 OH 6-(2-hydroxyethyl) A-2866 OH 7-(2-hydroxyethyl) A-2867 OH 4-(1-hydroxyethyl) A-2868 OH 5-(1-hydroxyethyl) A-2869 OH 6-(1-hydroxyethyl) A-2870 OH 7-(1-hydroxyethyl) A-2871 OH 4-(3-hydroxypropyl) A-2872 OH 5-(3-hydroxypropyl) A-2873 OH 6-(3-hydroxypropyl) A-2874 OH 7-(3-hydroxypropyl) A-2875 OH 4-(2-hydroxypropyl) A-2876 OH 5-(2-hydroxypropyl) A-2877 OH 6-(2-hydroxypropyl) A-2878 OH 7-(2-hydroxypropyl) A-2879 OH 4-(1-hydroxypropyl) A-2880 OH 5-(1-hydroxypropyl) A-2881 OH 6-(1-hydroxypropyl) A-2882 OH 7-(1-hydroxypropyl) A-2883 OH 4-aminomethyl A-2884 OH 5-aminomethyl A-2885 OH 6-aminomethyl A-2886 OH 7-aminomethyl A-2887 OH 4-(2-aminoethyl) A-2888 OH 5-(2-aminoethyl) A-2889 OH 6-(2-aminoethyl) A-2890 OH 7-(2-aminoethyl) A-2891 OH 4-(1-aminoethyl) A-2892 OH 5-(1-aminoethyl) A-2893 OH 6-(1-aminoethyl) A-2894 OH 7-(1-aminoethyl) A-2895 OH 4-(3-aminopropyl) A-2896 OH 5-(3-aminopropyl) A-2897 OH 6-(3-aminopropyl) A-2898 OH 7-(3-aminopropyl) A-2899 OH 4-(2-aminopropyl) A-2900 OH 5-(2-aminopropyl) A-2901 OH 6-(2-aminopropyl) A-2902 OH 7-(2-aminopropyl) A-2903 OH 4-(1-aminopropyl) A-2904 OH 5-(1-aminopropyl) A-2905 OH 6-(1-aminopropyl) A-2906 OH 7-(1-aminopropyl) A-2907 OH 4-COOH A-2908 OH 5-COOH A-2909 OH 6-COOH A-2910 OH 7-COOH A-2911 OH 4-COOCH.sub.3 A-2912 OH 5-COOCH.sub.3 A-2913 OH 6-COOCH.sub.3 A-2914 OH 7-COOCH.sub.3 A-2915 OH 4-COOCH.sub.2CH.sub.3 A-2916 OH 5-COOCH.sub.2CH.sub.3 A-2917 OH 6-COOCH.sub.2CH.sub.3 A-2918 OH 7-COOCH.sub.2CH.sub.3 A-2919 OH 4-COOCF.sub.3 A-2920 OH 5-COOCF.sub.3 A-2921 OH 6-COOCF.sub.3 A-2922 OH 7-COOCF.sub.3 A-2923 OH 4-CONH.sub.2 A-2924 OH 5-CONH.sub.2 A-2925 OH 6-CONH.sub.2 A-2926 OH 7-CONH.sub.2 A-2927 OH 4-CONHCH.sub.3 A-2928 OH 5-CONHCH.sub.3 A-2929 OH 6-CONHCH.sub.3 A-2930 OH 7-CONHCH.sub.3 A-2931 OH 4-CON(CH.sub.3).sub.2 A-2932 OH 5-CON(CH.sub.3).sub.2 A-2933 OH 6-CON(CH.sub.3).sub.2 A-2934 OH 7-CON(CH.sub.3).sub.2 A-2935 OH 4-CONHCH.sub.2CH.sub.3 A-2936 OH 5-CONHCH.sub.2CH.sub.3 A-2937 OH 6-CONHCH.sub.2CH.sub.3 A-2938 OH 7-CONHCH.sub.2CH.sub.3 A-2939 OH 4-CON(CH.sub.2CH.sub.3).sub.2 A-2940 OH 5-CON(CH.sub.2CH.sub.3).sub.2 A-2941 OH 6-CON(CH.sub.2CH.sub.3).sub.2 A-2942 OH 7-CON(CH.sub.2CH.sub.3).sub.2 A-2943 OH 4-A-1 A-2944 OH 5-A-1 A-2945 OH 6-A-1 A-2946 OH 7-A-1 A-2947 OH 4-A-2 A-2948 OH 5-A-2 A-2949 OH 6-A-2 A-2950 OH 7-A-2 A-2951 OH 4-A-3 A-2952 OH 5-A-3 A-2953 OH 6-A-3 A-2954 OH 7-A-3 A-2955 OH 4-A-4 A-2956 OH 5-A-4 A-2957 OH 6-A-4 A-2958 OH 7-A-4 A-2959 OH 4-A-5 A-2960 OH 5-A-5 A-2961 OH 6-A-5 A-2962 OH 7-A-5 A-2963 OH 4-A-6 A-2964 OH 5-A-6 A-2965 OH 6-A-6 A-2966 OH 7-A-6 A-2967 OH 4-A-7 A-2968 OH 5-A-7 A-2969 OH 6-A-7 A-2970 OH 7-A-7 A-2971 OH 4-A-8 A-2972 OH 5-A-8 A-2973 OH 6-A-8 A-2974 OH 7-A-8 A-2975 OH 4-A-9 A-2976 OH 5-A-9 A-2977 OH 6-A-9 A-2978 OH 7-A-9 A-2979 OH 4-A-10 A-2980 OH 5-A-10 A-2981 OH 6-A-10 A-2982 OH 7-A-10 A-2983 OH 4-A-11 A-2984 OH 5-A-11 A-2985 OH 6-A-11 A-2986 OH 7-A-11 A-2987 OH 4-A-12 A-2988 OH 5-A-12 A-2989 OH 6-A-12 A-2990 OH 7-A-12 A-2991 OH 4-A-13 A-2992 OH 5-A-13 A-2993 OH 6-A-13 A-2994 OH 7-A-13 A-2995 OH 4-A-14 A-2996 OH 5-A-14 A-2997 OH 6-A-14 A-2998 OH 7-A-14 A-2999 OH 4-A-15 A-3000 OH 5-A-15 A-3001 OH 6-A-15 A-3002 OH 7-A-15 A-3003 OH 4-A-16 A-3004 OH 5-A-16 A-3005 OH 6-A-16

A-3006 OH 7-A-16 A-3007 OH 4-A-17 A-3008 OH 5-A-17 A-3009 OH 6-A-17 A-3010 OH 7-A-17 A-3011 OH 4-A-18 A-3012 OH 5-A-18 A-3013 OH 6-A-18 A-3014 OH 7-A-18 A-3015 OH 4-A-19 A-3016 OH 5-A-19 A-3017 OH 6-A-19 A-3018 OH 7-A-19 A-3019 OH 4-A-20 A-3020 OH 5-A-20 A-3021 OH 6-A-20 A-3022 OH 7-A-20 A-3023 OH 4-A-21 A-3024 OH 5-A-21 A-3025 OH 6-A-21 A-3026 OH 7-A-21 A-3027 OH 4-A-22 A-3028 OH 5-A-22 A-3029 OH 6-A-22 A-3030 OH 7-A-22 A-3031 OH 4-A-23 A-3032 OH 5-A-23 A-3033 OH 6-A-23 A-3034 OH 7-A-23 A-3035 OH 4-A-24 A-3036 OH 5-A-24 A-3037 OH 6-A-24 A-3038 OH 7-A-24 A-3039 OH 4-A-25 A-3040 OH 5-A-25 A-3041 OH 6-A-25 A-3042 OH 7-A-25 A-3043 OH 4-A-26 A-3044 OH 5-A-26 A-3045 OH 6-A-26 A-3046 OH 7-A-26 A-3047 OH 4-A-27 A-3048 OH 5-A-27 A-3049 OH 6-A-27 A-3050 OH 7-A-27 A-3051 OH 4-A-28 A-3052 OH 5-A-28 A-3053 OH 6-A-28 A-3054 OH 7-A-28 A-3055 OH 4-A-29 A-3056 OH 5-A-29 A-3057 OH 6-A-29 A-3058 OH 7-A-29 A-3059 OH 4-A-30 A-3060 OH 5-A-30 A-3061 OH 6-A-30 A-3062 OH 7-A-30 A-3063 OH 4-A-31 A-3064 OH 5-A-31 A-3065 OH 6-A-31 A-3066 OH 7-A-31 A-3067 OH 4-A-32 A-3068 OH 5-A-32 A-3069 OH 6-A-32 A-3070 OH 7-A-32 A-3071 OH 4-A-33 A-3072 OH 5-A-33 A-3073 OH 6-A-33 A-3074 OH 7-A-33 A-3075 OH 4-A-34 A-3076 OH 5-A-34 A-3077 OH 6-A-34 A-3078 OH 7-A-34 A-3079 OH 4-A-35 A-3080 OH 5-A-35 A-3081 OH 6-A-35 A-3082 OH 7-A-35 A-3083 OH 4-A-36 A-3084 OH 5-A-36 A-3085 OH 6-A-36 A-3086 OH 7-A-36 A-3087 OH 4-A-37 A-3088 OH 5-A-37 A-3089 OH 6-A-37 A-3090 OH 7-A-37 A-3091 OH 4-A-38 A-3092 OH 5-A-38 A-3093 OH 6-A-38 A-3094 OH 7-A-38 A-3095 OH 4-A-39 A-3096 OH 5-A-39 A-3097 OH 6-A-39 A-3098 OH 7-A-39 A-3099 OH 4-A-40 A-3100 OH 5-A-40 A-3101 OH 6-A-40 A-3102 OH 7-A-40 A-3103 OH 4-A-41 A-3104 OH 5-A-41 A-3105 OH 6-A-41 A-3106 OH 7-A-41 A-3107 OH 4-A-42 A-3108 OH 5-A-42 A-3109 OH 6-A-42 A-3110 OH 7-A-42 A-3111 OH 4-A-43 A-3112 OH 5-A-43 A-3113 OH 6-A-43 A-3114 OH 7-A-43 A-3115 OH 4-A-44 A-3116 OH 5-A-44 A-3117 OH 6-A-44 A-3118 OH 7-A-44 A-3119 OH 4-A-45 A-3120 OH 5-A-45 A-3121 OH 6-A-45 A-3122 OH 7-A-45 A-3123 OH 4-A-46 A-3124 OH 5-A-46 A-3125 OH 6-A-46 A-3126 OH 7-A-46 A-3127 OH 4-A-47 A-3128 OH 5-A-47 A-3129 OH 6-A-47 A-3130 OH 7-A-47 A-3131 OH 4-A-48 A-3132 OH 5-A-48 A-3133 OH 6-A-48 A-3134 OH 7-A-48 A-3135 OH 4-A-49 A-3136 OH 5-A-49 A-3137 OH 6-A-49 A-3138 OH 7-A-49 A-3139 OH 4-A-50 A-3140 OH 5-A-50 A-3141 OH 6-A-50 A-3142 OH 7-A-50 A-3143 OH 4-A-51 A-3144 OH 5-A-51 A-3145 OH 6-A-51 A-3146 OH 7-A-51 A-3147 OH 4-A-52 A-3148 OH 5-A-52 A-3149 OH 6-A-52 A-3150 OH 7-A-52 A-3151 OH 4-A-53 A-3152 OH 5-A-53 A-3153 OH 6-A-53 A-3154 OH 7-A-53 A-3155 OH 4-A-54 A-3156 OH 5-A-54 A-3157 OH 6-A-54 A-3158 OH 7-A-54 A-3159 OH 4-A-55 A-3160 OH 5-A-55 A-3161 OH 6-A-55 A-3162 OH 7-A-55 A-3163 OH 4-A-56 A-3164 OH 5-A-56 A-3165 OH 6-A-56 A-3166 OH 7-A-56 A-3167 OH 4-A-57 A-3168 OH 5-A-57 A-3169 OH 6-A-57 A-3170 OH 7-A-57 A-3171 OH 4-A-58 A-3172 OH 5-A-58 A-3173 OH 6-A-58 A-3174 OH 7-A-58 A-3175 OH 4-A-59 A-3176 OH 5-A-59 A-3177 OH 6-A-59 A-3178 OH 7-A-59 A-3179 OH 4-A-60 A-3180 OH 5-A-60 A-3181 OH 6-A-60 A-3182 OH 7-A-60 A-3183 OH 4-A-61 A-3184 OH 5-A-61 A-3185 OH 6-A-61 A-3186 OH 7-A-61 A-3187 OH 4-A-62 A-3188 OH 5-A-62 A-3189 OH 6-A-62 A-3190 OH 7-A-62 A-3191 OH 4-A-63 A-3192 OH 5-A-63 A-3193 OH 6-A-63 A-3194 OH 7-A-63 A-3195 OH 4-A-64 A-3196 OH 5-A-64 A-3197 OH 6-A-64 A-3198 OH 7-A-64 A-3199 OH 4-A-65 A-3200 OH 5-A-65 A-3201 OH 6-A-65 A-3202 OH 7-A-65 A-3203 OH 4-A-66 A-3204 OH 5-A-66 A-3205 OH 6-A-66 A-3206 OH 7-A-66 A-3207 OH 4-A-67 A-3208 OH 5-A-67 A-3209 OH 6-A-67 A-3210 OH 7-A-67 A-3211 OH 4-A-68 A-3212 OH 5-A-68 A-3213 OH 6-A-68 A-3214 OH 7-A-68 A-3215 OH 4-A-69 A-3216 OH 5-A-69 A-3217 OH 6-A-69 A-3218 OH 7-A-69 A-3219 OH 4-A-70 A-3220 OH 5-A-70 A-3221 OH 6-A-70 A-3222 OH 7-A-70 A-3223 OH 4-A-71 A-3224 OH 5-A-71 A-3225 OH 6-A-71 A-3226 OH 7-A-71 A-3227 OH 4-A-72 A-3228 OH 5-A-72 A-3229 OH 6-A-72 A-3230 OH 7-A-72 A-3231 OH 4-A-73 A-3232 OH 5-A-73 A-3233 OH 6-A-73 A-3234 OH 7-A-73 A-3235 OH 4-A-74 A-3236 OH 5-A-74 A-3237 OH 6-A-74 A-3238 OH 7-A-74 A-3239 OH 4-A-75 A-3240 OH 5-A-75 A-3241 OH 6-A-75 A-3242 OH 7-A-75 A-3243 OH 4-A-76 A-3244 OH 5-A-76 A-3245 OH 6-A-76 A-3246 OH 7-A-76 A-3247 OH 4-A-77 A-3248 OH 5-A-77 A-3249 OH 6-A-77 A-3250 OH 7-A-77 A-3251 OH 4-A-78 A-3252 OH 5-A-78 A-3253 OH 6-A-78 A-3254 OH 7-A-78 A-3255 OH 4-A-79 A-3256 OH 5-A-79

A-3257 OH 6-A-79 A-3258 OH 7-A-79 A-3259 OH 4-A-80 A-3260 OH 5-A-80 A-3261 OH 6-A-80 A-3262 OH 7-A-80 A-3263 OH 4-A-81 A-3264 OH 5-A-81 A-3265 OH 6-A-81 A-3266 OH 7-A-81 A-3267 OH 4-A-82 A-3268 OH 5-A-82 A-3269 OH 6-A-82 A-3270 OH 7-A-82 A-3271 OH 4-A-83 A-3272 OH 5-A-83 A-3273 OH 6-A-83 A-3274 OH 7-A-83 A-3275 OH 4-A-84 A-3276 OH 5-A-84 A-3277 OH 6-A-84 A-3278 OH 7-A-84 A-3279 OH 4-A-85 A-3280 OH 5-A-85 A-3281 OH 6-A-85 A-3282 OH 7-A-85 A-3283 OH 4-A-86 A-3284 OH 5-A-86 A-3285 OH 6-A-86 A-3286 OH 7-A-86 A-3287 OH 4-A-87 A-3288 OH 5-A-87 A-3289 OH 6-A-87 A-3290 OH 7-A-87 A-3291 OH 4-A-88 A-3292 OH 5-A-88 A-3293 OH 6-A-88 A-3294 OH 7-A-88 A-3295 OH 4-A-89 A-3296 OH 5-A-89 A-3297 OH 6-A-89 A-3298 OH 7-A-89 A-3299 OH 4-A-90 A-3300 OH 5-A-90 A-3301 OH 6-A-90 A-3302 OH 7-A-90 A-3303 OH 4-A-91 A-3304 OH 5-A-91 A-3305 OH 6-A-91 A-3306 OH 7-A-91 A-3307 OH 4-A-92 A-3308 OH 5-A-92 A-3309 OH 6-A-92 A-3310 OH 7-A-92 A-3311 OH 4-A-93 A-3312 OH 5-A-93 A-3313 OH 6-A-93 A-3314 OH 7-A-93 A-3315 OH 4-A-94 A-3316 OH 5-A-94 A-3317 OH 6-A-94 A-3318 OH 7-A-94 A-3319 OH 4-A-95 A-3320 OH 5-A-95 A-3321 OH 6-A-95 A-3322 OH 7-A-95 A-3323 OH 4-A-96 A-3324 OH 5-A-96 A-3325 OH 6-A-96 A-3326 OH 7-A-96 A-3327 OH 4-A-97 A-3328 OH 5-A-97 A-3329 OH 6-A-97 A-3330 OH 7-A-97 A-3331 OH 4-A-98 A-3332 OH 5-A-98 A-3333 OH 6-A-98 A-3334 OH 7-A-98 A-3335 OH 4-A-99 A-3336 OH 5-A-99 A-3337 OH 6-A-99 A-3338 OH 7-A-99 A-3339 OH 4-A-100 A-3340 OH 5-A-100 A-3341 OH 6-A-100 A-3342 OH 7-A-100 A-3343 OH 4-A-101 A-3344 OH 5-A-101 A-3345 OH 6-A-101 A-3346 OH 7-A-101 A-3347 OH 4-A-102 A-3348 OH 5-A-102 A-3349 OH 6-A-102 A-3350 OH 7-A-102 A-3351 OH 4-A-103 A-3352 OH 5-A-103 A-3353 OH 6-A-103 A-3354 OH 7-A-103 A-3355 OH 4-A-104 A-3356 OH 5-A-104 A-3357 OH 6-A-104 A-3358 OH 7-A-104 A-3359 OH 4-A-104 A-3360 OH 5-A-104 A-3361 OH 6-A-104 A-3362 OH 7-A-104 A-3363 OH 4-A-105 A-3364 OH 5-A-105 A-3365 OH 6-A-105 A-3366 OH 7-A-105 A-3367 OH 4-A-106 A-3368 OH 5-A-106 A-3369 OH 6-A-106 A-3370 OH 7-A-106 A-3371 OH 4-A-107 A-3372 OH 5-A-107 A-3373 OH 6-A-107 A-3374 OH 7-A-107 A-3375 OH 4-A-108 A-3376 OH 5-A-108 A-3377 OH 6-A-108 A-3378 OH 7-A-108 A-3379 OH 4-A-109 A-3380 OH 5-A-109 A-3381 OH 6-A-109 A-3382 OH 7-A-109 A-3383 OH 4-A-110 A-3384 OH 5-A-110 A-3385 OH 6-A-110 A-3386 OH 7-A-110 A-3387 OH 4-A-111 A-3388 OH 5-A-111 A-3389 OH 6-A-111 A-3390 OH 7-A-111

[0715] Among the above compounds, preference is given to compounds of formulae I.1 to I.21, I.37 to I.57, I.73 to I.93 and I.109 to I.129. More preference is given to compounds I.1 to I.6, I.10 to I.17, I.37 to I.42, I.46 to I.53, I.73 to I.78, I.82 to I.89, I.109 to I.114 and I.118 to I.125. Even more preference is given to compounds of formulae I.1, I.2, I.3, I.10, I.11, I.12, I.13, I.14, I.15, I.16, I.17, I.37, I.38, I.39, I.46, I.47, I.48, I.49, I.50, I.51, I.52, I.53, I.74, I.77, I.83, I.84, I.87, I.88, I.109, I.110, I.111, I.113, I.118, I.119, I.120 and I.124. Particular preference is given to compounds of formulae I.10, I.11, I.12, I.13, I.46, I.47, I.48, I.49, I.110 and I.120. Specific preference is given to compounds of formulae I.13, I.46, I.49, I.110 and I.120.

[0716] The compounds of the present invention can be prepared by analogy to routine techniques a skilled person is familiar with. In particular, the compounds of the formula IA and IB can be prepared according to the following schemes, wherein the variables, if not stated otherwise, are as defined above. In the below schemes, compounds of formula IA are expressed as target molecules. However, the same reactions apply to the syntheses of compounds IB.

[0717] Compounds of formula IA can be prepared by reacting the indolol compound 1 with the the pyridyl derivative 2, where X is Cl or Br. The reaction can be carried out under the conditions of a Heck reaction, via Pd-catalysed cross coupling, generally in the presence of a base. Alternatively, 1 and 2 can be reacted in a nucleophilic aromatic substitution reaction in the presence of a strong, non-nucleophilic base, such as NaH, LDA or preferably sodium bis(trimethylsilyl)amide (NaHMDS). If suitable, the nucleophilic aromatic substitution reaction can also be carried out with the N-oxide of the pyridyl compound 2.

##STR00047##

[0718] Compounds 1 are either commercially available or can be synthesized by procedures generally known in the art. For example, generally known substitution reactions for introducing different substituents R.sup.1 (different from hydrogen) can be applied. For instance, a compound 1 wherein at least one substituent R.sup.1 is hydrogen can be halogenated, for example by reaction with N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide, to give a compound 1 wherein this R.sup.1 is Cl, Br or I. This in turn can be reacted with CuCN to give a compound 1 wherein this R.sup.1 is CN. An exemplary reaction pattern using indolone as a scaffold for compound 1 is shown in scheme 2.

##STR00048##

[0719] If R.sup.1 is Ar, this substituent can be introduced via a Suzuki coupling reaction, as shown in schemes 3 and 4 exemplarily for indolone as a scaffold for compound 1. BRR' is a boronic acid residue [B(OH).sub.2] or a boronic ester group, such as B(O-t-butyl).sub.2, B(--O--C(CH.sub.3).sub.2--C(CH.sub.3).sub.2--O--) and the like. The reaction is carried in the presence of a palladium catalyst, especially a palladium phosphane catalyst, such as tetrakis(triphenylphosphine) palladium(0), and of a base, such as NaOH, Na.sub.2CO.sub.3, NaHCO.sub.3, Na.sub.3PO.sub.4, sodium methanolate, sodium ethanolate and the like.

##STR00049##

##STR00050##

[0720] Compounds 2 are either commercially available or can be synthesized by procedures generally known in the art.

[0721] Compounds 2, wherein R.sup.3 and R.sup.4 form together a group --(CH.sub.2).sub.3--C(O)-- (compound 2.1), can for example be prepared by reacting 3-aminocyclohex-2-enone 9 with an alkylpropiolate, e.g. methylpropiolate 10, and subsequently halogenating the keto/enol group of 11 with a halogenating agent, such as POCl.sub.3, as shown in scheme 5. The same reaction sequence can be applied for producing compounds, wherein R.sup.3 and R.sup.4 form together a group --(CH.sub.2).sub.2--C(O)-- by using 3-aminocyclopent-2-enone instead of 9, for producing compounds, wherein R.sup.3 and R.sup.4 form together a group --C(O)--(CH.sub.2).sub.3-- by using 2-aminocyclohex-2-enone instead of 9, for producing compounds, wherein R.sup.3 and R.sup.4 form together a group --C(O)--(CH.sub.2).sub.2-- by using 2-aminocyclopent-2-enone instead of 9, etc.

##STR00051##

[0722] For producing compounds 2, wherein R.sup.4 and R.sup.5 form together a group --C(O)--O--CH.sub.2-- or --CH.sub.2--NR.sup.c--CH.sub.2--, the reaction sequence shown in scheme 6 can be used. The carboxyl group of 12 is suitably first converted into its acid chloride, e.g. via reaction with thionyl chloride or oxalylchloride, and the acid chloride is then reacted with diisopropylamine to the amide 13. Deprotonation with LDA in the activated 4-position yields a carbanion which nucleophilicaly attacks dimethylformamide to give the amide-aldehyde 14. Reduction of the aldehyde group, e.g. with NaBH.sub.4, and subsequent esterification leads to the furanone 15. If desired, this can be subjected to a reductive ring-opening reaction to the dimethylol 16, which is converted into the respective dimethylchloride 17. Reaction of 17 with a primary amine R--NH.sub.2, where advantageously R is a group which can be easily removed, such as benzyl or PMB (PMB=para-methoxybenzyl), yields the pyrrolidinypyridine 18, which is deprotected to 19. Deprotection is carried out depending on the group R, e.g. with HCl or 1-chloroethylchloroformiate if R is benzyl or a substituted benzyl, such as PMB.

##STR00052##

[0723] Compounds 2, wherein R.sup.5 and R.sup.6 form together a group --C(O)--O--CH.sub.2-- or --CH.sub.2--NR.sup.c--CH.sub.2--, can be prepared in an analogous reaction sequence, however starting from 2-chloro-nicotinic acid.

[0724] Compounds 2, wherein R.sup.4 and R.sup.5 form together a group --(CH.sub.2).sub.4--, can be prepared by the reaction sequence shown in scheme 7. 20 is subjected to a ring-closing reaction with ammonium carbonate under heating (230.degree. C.), as described in Chemische Berichte 1948, 81, 279-285. Alternatively, 21 is reacted according to the procedure described in J. Chem. Soc. 1932, 2426-2430 to 22. The diol 22 is then converted into the respective dichloride 23, e.g. with phosphoryl chloride. Reaction with zinc powder and aqueous HCl as described in Chemische Berichte 1948, 81, 279-285 finally yields 24.

##STR00053##

[0725] Compounds 2, wherein R.sup.4 and R.sup.5 form together a group --CH.sub.2--O--CH.sub.2-- or --CH.sub.2--O--CH.sub.2--CH.sub.2--, can be prepared as shown in scheme 8. 25 or 28 are reacted with triethylsilane, Mn(IV) oxide and trifluoroacetic acid as described in Tetrahedron Lett. 2008, 49(47), 6701-6703. Removal of one chlorine atom is accomplished using zinc powder and aqueous HCl, as described in Chemische Berichte 1948, 81, 279-285.

##STR00054##

[0726] Compounds 2, wherein R.sup.4 and R.sup.5 form together a group --CH.sub.2--CH.sub.2--NR.sup.c--C(O)-- are known and described, for example, in EP-A-1180514. Compounds 2, wherein R.sup.4 and R.sup.5 form together a group --CH.sub.2--CH.sub.2--NR.sup.c--CH.sub.2--, can be prepared by reducing compound 31, as shown in scheme 9. Reduction can be carried out, for example, by using a borane reduction agent, such as 9-BBN. Compound 31 is known from EP-A-1180514.

##STR00055##

[0727] Compounds IA can be converted into compounds IB, wherein R.sup.2 is fluorine, by reaction of IA with a suitable fluorinating agent, such as 1-fluoro-2,4,6-trimethylpyridinium triflate in the presence of a suitable base, such as n-butyllithium or sodium bis(trimethylsilyl)amide in a suitable solvent, such as tetrahydrofuran or dioxane at from -40.degree. C. to 80.degree. C.

[0728] If not indicated otherwise, the above-described reactions are generally carried out in a solvent at temperatures between room temperature and the boiling temperature of the solvent employed. Alternatively, the activation energy which is required for the reaction can be introduced into the reaction mixture using microwaves, something which has proved to be of value, in particular, in the case of the reactions catalyzed by transition metals (with regard to reactions using microwaves, see Tetrahedron 2001, 57, p. 9199 ff. p. 9225 ff. and also, in a general manner, "Microwaves in Organic Synthesis", Andre Loupy (Ed.), Wiley-VCH 2002.

[0729] The acid addition salts of compounds IA and IB are prepared in a customary manner by mixing the free base with a corresponding acid, where appropriate in solution in an organic solvent, for example a lower alcohol, such as methanol, ethanol or propanol, an ether, such as methyl tert-butyl ether or diisopropyl ether, a ketone, such as acetone or methyl ethyl ketone, or an ester, such as ethyl acetate.

[0730] The present invention moreover relates to compounds of formula I as defined above, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope (e.g., hydrogen by deuterium, .sup.13C by .sup.13 C, .sup.14N by .sup.15N, .sup.16O by .sup.18O) and preferably wherein at least one hydrogen atom has been replaced by a deuterium atom.

[0731] Of course, the compounds according to the invention contain more of the respective isotope than this naturally occurs and thus is anyway present in the compounds I.

[0732] Stable isotopes (e.g., deuterium, .sup.13C, .sup.15N, .sup.18O) are nonradioactive isotopes which contain one additional neutron than the normally abundant isotope of the respective atom. Deuterated compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the non deuterated parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

[0733] Incorporation of a heavy atom particularly substitution of deuterium for hydrogen, can give rise to an isotope effect that could alter the pharmacokinetics of the drug. This effect is usually insignificant if the label is placed at a metabolically inert position of the molecule.

[0734] Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These changes may influence the fate of the drug at different steps along its passage through the body. Absorption, distribution, metabolism or excretion can be changed. Absorption and distribution are processes that depend primarily on the molecular size and the lipophilicity of the substance. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction.

[0735] Drug metabolism can give rise to large isotopic effect if the breaking of a chemical bond to a deuterium atom is the rate limiting step in the process. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. In any reaction in which the breaking of this bond is the rate limiting step, the reaction will proceed slower for the molecule with the heavy isotope due to "kinetic isotope effect". A reaction involving breaking a C-D bond can be up to 700 percent slower than a similar reaction involving breaking a C--H bond. If the C-D bond is not involved in any of the steps leading to the metabolite, there may not be any effect to alter the behavior of the drug. If a deuterium is placed at a site involved in the metabolism of a drug, an isotope effect will be observed only if breaking of the C-D bond is the rate limiting step. There is evidence to suggest that whenever cleavage of an aliphatic C--H bond occurs, usually by oxidation catalyzed by a mixed-function oxidase, replacement of the hydrogen by deuterium will lead to observable isotope effect. It is also important to understand that the incorporation of deuterium at the site of metabolism slows its rate to the point where another metabolite produced by attack at a carbon atom not substituted by deuterium becomes the major pathway a process called "metabolic switching".

[0736] Deuterium tracers, such as deuterium-labeled drugs and doses, in some cases repeatedly, of thousands of milligrams of deuterated water, are also used in healthy humans of all ages, including neonates and pregnant women, without reported incident (e.g. Pons G and Rey E, Pediatrics 1999 104: 633; Coward W A et al., Lancet 1979 7: 13; Schwarcz H P, Control. Clin. Trials 1984 5(4 Suppl): 573; Rodewald L E et al., J. Pediatr. 1989 114: 885; Butte N F et al. Br. J. Nutr. 1991 65: 3; MacLennan A H et al. Am. J. Obstet Gynecol. 1981 139: 948). Thus, it is clear that any deuterium released, for instance, during the metabolism of compounds of this invention poses no health risk.

[0737] The weight percentage of hydrogen in a mammal (approximately 9%) and natural abundance of deuterium (approximately 0.015%) indicates that a 70 kg human normally contains nearly a gram of deuterium. Furthermore, replacement of up to about 15% of normal hydrogen with deuterium has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Higher deuterium concentrations, usually in excess of 20%, can be toxic in animals. However, acute replacement of as high as 15%-23% of the hydrogen in humans' fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in "Dosimetry & Treatment Planning for Neutron Capture Therapy", Zamenhof R, Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab. 23: 251 (1997)).

[0738] Increasing the amount of deuterium present in a compound above its natural abundance is called enrichment or deuterium-enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %.

[0739] The hydrogens present on a particular organic compound have different capacities for exchange with deuterium. Certain hydrogen atoms are easily exchangeable under physiological conditions and, if replaced by deuterium atoms, it is expected that they will readily exchange for protons after administration to a patient. Certain hydrogen atoms may be exchanged for deuterium atoms by the action of a deuteric acid such as D.sub.2SO.sub.4/D.sub.2O. Alternatively, deuterium atoms may be incorporated in various combinations during the synthesis of compounds of the invention. Certain hydrogen atoms are not easily exchangeable for deuterium atoms. However, deuterium atoms at the remaining positions may be incorporated by the use of deuterated starting materials or intermediates during the construction of compounds of the invention.

[0740] Deuterated and deuterium-enriched compounds of the invention can be prepared by using known methods described in the literature. Such methods can be carried out utilizing corresponding deuterated and optionally, other isotope-containing reagents and/or intermediates to synthesize the compounds delineated herein, or invoking standard synthetic protocols known in the art for introducing isotopic atoms to a chemical structure. Relevant procedures and intermediates are disclosed, for instance in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. Pat. Nos. 7,538,189; 7,534,814; 7,531,685; 7,528,131; 7,521,421; 7,514,068; 7,511,013; and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; 20090082471, the methods are hereby incorporated by reference.

[0741] The present invention further relates to a pharmaceutical composition comprising at least one compound of formulae IA or IB, a stereoisomer, prodrug, tautomer and/or physiologically tolerated acid addition salt thereof and optionally at least one physiologically acceptable carrier and/or auxiliary substance.

[0742] The invention also relates to the use of the compounds of formulae IA or IB or of a stereoisomer, prodrug, tautomer or physiologically tolerated acid addition salt thereof for the preparation of a medicament for the treatment of a disorder susceptible to the treatment with a compound that modulates, preferably inhibits, the activity of glycogen synthase kinase 3.beta..

[0743] Furthermore, the invention relates to a method for treating a medical disorder susceptible to treatment with a compound that modulates glycogen synthase kinase 3.beta. activity, said method comprising administering an effective amount of at least one compound of formulae IA or IB or of a stereoisomer, prodrug, tautomer or physiologically tolerated acid addition salt thereof or of a pharmaceutical composition as defined above to a subject in need thereof.

[0744] The compounds of the of formulae IA or IB according to the present invention, as well as the stereoisomers, the tautomers, the prodrugs and physiologically tolerated acid addition salts thereof, are capable of modulating the activity on glycogen synthase kinase 3.beta.. In particular, the compounds of the of formulae IA or IB, as well as the stereoisomers, the tautomers, the prodrugs and physiologically tolerated acid addition salts thereof, have an inhibitory activity on glycogen synthase kinase 3.beta.. Amongst the compounds of formulae IA or IB those are preferred which achieve effective inhibition at low concentrations. In particular, compounds of the formulae IA and IB are preferred which inhibit glycogen synthase kinase 3.beta. at a level of IC.sub.50<1 .mu.Mol, more preferably at a level of IC.sub.50<0. 5 .mu.Mol, particularly preferably at a level of IC.sub.50<0.2 .mu.Mol and most preferably at a level of IC.sub.50<0.1 .mu.Mol.

[0745] Therefore the compounds of the of formulae IA or IB according to the present invention, their stereoisomers, tautomers, their prodrugs and their physiologically tolerated acid addition salts are useful for the treatment of a medical disorder susceptible to treatment with a compound that modulates glycogen synthase kinase 3.beta. activity. As mentioned above, diseases caused by abnormal GSK-3.beta. activity and which thus can be treated by supplying the compound of the formulae IA and IB, a steroisomer, tautomer, prodrug and/or a physiologically tolerated acid addition salt thereof, include in particular neurodegenerative diseases such as Alzheimer's disease. In addition, the compounds of the present invention are also useful for treatment of other neurodegenerative diseases such as Parkinson's disease, tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy, argyophilic brain disease) and other dementia including vascular dementia; acute stroke and others traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration); brain and spinal cord trauma; peripheral neuropathies; bipolar disorders, retinopathies and glaucoma. In addition, the compounds of the present invention are also useful for treatment of schizophrenia.

[0746] Diseases which can be treated by supplying the compound of the of formulae IA or IB, a steroisomer, tautomer, prodrug and/or a physiologically tolerated acid addition salt thereof, include furthermore inflammatory diseases, such as rheumatoid arthritis and osteoarthritis.

[0747] Within the meaning of the invention, a treatment also includes a preventive treatment (prophylaxis), in particular as relapse prophylaxis or phase prophylaxis, as well as the treatment of acute or chronic signs, symptoms and/or malfunctions. The treatment can be orientated symptomatically, for example as the suppression of symptoms. It can be effected over a short period, be orientated over the medium term or can be a long-term treatment, for example within the context of a maintenance therapy.

[0748] Within the context of the treatment, the use according to the invention of the compounds of the formulae IA or IB involves a method. In this method, an effective quantity of one or more compounds IA or IB, a steroisomer, tautomer, prodrug or physiologically tolerable acid addition salt thereof, as a rule formulated in accordance with pharmaceutical and veterinary practice, is administered to the individual to be treated, preferably a mammal, in particular a human being, productive animal or domestic animal. Whether such a treatment is indicated, and in which form it is to take place, depends on the individual case and is subject to medical assessment (diagnosis) which takes into consideration signs, symptoms and/or malfunctions which are present, the risks of developing particular signs, symptoms and/or malfunctions, and other factors.

[0749] As a rule, the treatment is effected by means of single or repeated daily administration, where appropriate together, or alternating, with other active compounds or active compound-containing preparations such that a daily dose of preferably from about 0.1 to 1000 mg/kg of bodyweight, in the case of oral administration, or of from about 0.1 to 100 mg/kg of bodyweight, in the case of parenteral administration, is supplied to an individual to be treated.

[0750] The invention also relates to pharmaceutical compositions for treating an individual, preferably a mammal, in particular a human being, productive animal or domestic animal. Thus, the compounds according to the invention are customarily administered in the form of pharmaceutical compositions which comprise a pharmaceutically acceptable excipient together with at least one compound according to the invention and, where appropriate, other active compounds. These compositions can, for example, be administered orally, rectally, transdermally, subcutaneously, intravenously, intramuscularly or intranasally.

[0751] Examples of suitable pharmaceutical formulations are solid medicinal forms, such as powders, granules, tablets, in particular film tablets, lozenges, sachets, cachets, sugarcoated tablets, capsules, such as hard gelatin capsules and soft gelatin capsules, suppositories or vaginal medicinal forms, semisolid medicinal forms, such as ointments, creams, hydrogels, pastes or plasters, and also liquid medicinal forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection preparations and infusion preparations, and eyedrops and eardrops. Implanted release devices can also be used for administering inhibitors according to the invention. In addition, it is also possible to use liposomes or microspheres.

[0752] When producing the pharmaceutical compositions, the compounds according to the invention are optionally mixed or diluted with one or more excipients. Excipients can be solid, semisolid or liquid materials which serve as vehicles, carriers or medium for the active compound.

[0753] Suitable excipients are listed in the specialist medicinal monographs. In addition, the formulations can comprise pharmaceutically acceptable carriers or customary auxiliary substances, such as glidants; wetting agents; emulsifying and suspending agents; preservatives; antioxidants; antiirritants; chelating agents; coating auxiliaries; emulsion stabilizers; film formers; gel formers; odor masking agents; taste corrigents; resin; hydrocolloids; solvents; solubilizers; neutralizing agents; diffusion accelerators; pigments; quaternary ammonium compounds; refatting and overfatting agents; raw materials for ointments, creams or oils; silicone derivatives; spreading auxiliaries; stabilizers; sterilants; suppository bases; tablet auxiliaries, such as binders, fillers, glidants, disintegrants or coatings; propellants; drying agents; opacifiers; thickeners; waxes; plasticizers and white mineral oils. A formulation in this regard is based on specialist knowledge as described, for example, in Fiedler, H. P., Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik and angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy, cosmetics and related fields], 4.sup.th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996.

[0754] The following examples serve to explain the invention without limiting it.

EXAMPLES

[0755] The compounds were either characterized via proton-NMR in d.sub.6-dimethylsulfoxide or d-chloroform on a 400 MHz or 500 MHz NMR instrument (Bruker AVANCE), or by mass spectrometry, generally recorded via HPLC-MS in a fast gradient on C18-material (electrospray-ionisation (ESI) mode), or melting point.

[0756] The magnetic nuclear resonance spectral properties (NMR) refer to the chemical shifts (8) expressed in parts per million (ppm). The relative area of the shifts in the .sup.1H-NMR spectrum corresponds to the number of hydrogen atoms for a particular functional type in the molecule. The nature of the shift, as regards multiplicity, is indicated as singlet (s), broad singlet (s. br.), doublet (d), broad doublet (d br.), triplet (t), broad triplet (t br.), quartet (q), quintet (quint.) and multiplet (m).

Abbreviations

[0757] DMSO dimethylsulfoxide

[0758] DCM dichloromethane

[0759] DMF dimethylformamide

[0760] MeOH methanol

[0761] EtOAc ethylacetate

[0762] THF tetrahydrofurane

[0763] TBDMS tert-butyldimethylsilyl

[0764] TBFA tert-butylammonium fluoride

[0765] RT room temperature

[0766] d days

I. Preparation Examples

Example 1

3-(5-Hydroxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonitrile

##STR00056##

[0767] 1.1 5-(tert-Butyldimethylsilyloxy)-2-chloro-5,6,7,8-tetrahydroquino- line

[0768] A solution of 2-chloro-5,6,7,8-tetrahydroquinolin-5-ol (500 mg, 2.72 mmol) in DMF (10 mL) was treated with imidazole (260 mg, 3.81 mmol). After complete dissolution TBDMS-CI was added and the resulting mixture was stirred at RT for 16 h. The reaction mixture was diluted with EtOAc (40 mL) and was washed with brine (5x). The organic layer was collected, dried with Na.sub.2SO.sub.4, filtered, and the solvent was evaporated at reduced pressure yielding the titled compound as an oil. Amount 760 mg. Yield 94%.

[0769] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 0.16 (d, 6H), 0.89 (s, 9H), 1.70 (m, 1H), 1.78 (m, 1H), 1.95 (m, 2H), 2.79 (m, 2H), 4.84 (dd, 1H), 7.31 (d, 1H), 7.66 (d, 1H); MS (ES-API) m/z 298.1 (M+H.sup.+, 100%).

1.2 3-(5-(tert-Butyldimethylsilyloxy)-5,6,7,8-tetrahydroquinolin-2-yl)-2-o- xoindoline-5-carbonitrile

[0770] To a suspension of 2-oxoindoline-5-carbonitrile (30 mg, 0.190 mmol) in THF placed in a microwave vial were added sequentially 5-(tert-butyldimethylsilyloxy)-2-chloro-5,6,7,8-tetrahydroquinoline (67.8 mg, 0.228 mmol), K.sub.2CO.sub.3 (52.4 mg, 0.379 mmol), X-PHOS (7.23 mg, 0.015 mmol), and Pd.sub.2(dba).sub.3 (3.47 mg, 3.79 .mu.mol). The vial was sealed and flushed with argon. The mixture was heated in a microwave oven at 80.degree. C. for 95 min. The mixture was cooled to RT and diluted with water and ethyl acetate. The organic layer was separated and the remaining aqueous layer was extracted with dichloromethane. The combined dichloromethane extracts were dried over sodium sulfate, filtered, and evaporated to dryness. Amount 32 mg. Yield 40%.

[0771] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 0.19 (d, 6H), 0.92 (s, 9H), 1.73 (m, 1H), 1.81 (m, 1H), 1.97 (m, 2H), 2.79 (m, 1H), 2.87 (m, 1H), 4.79 (m, 1H), 7.04 (dd, 1H), 7.29 (dd, 1H), 7.74 (m, 2H), 7.92 (s, 1H), 10.90 (s, 1H)

[0772] MS (ES-API) m/z 420.2 (M+H.sup.+, 100%).

1.3 3-(5-Hydroxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonit- rile

[0773] A suspension of 3-(5-(tert-butyldimethylsilyloxy)-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoi- ndoline-5-carbonitrile (26 mg, 0.062 mmol) in tetrahydrofuran (5 mL) was cooled to 0.degree. C. To this mixture was added dropwise a 1.0M solution of TBAF in THF (0.124 ml, 0.124 mmol) resulting in a clear yellow solution. The reaction was stirred for 1 h at 0.degree. C. and then warmed to RT. After 3 h another portion of TBAF (1.0M in THF, 0.124 ml, 0.124 mmol) was added and the reaction was stirred at RT for 16 h. The mixture was diluted with ethyl acetate and the organic layer was washed with water (2x) and brine (1x). The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, DCM/MeOH) yielding a yellow solid. Amount 11 mg. Yield 59%.

[0774] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.75 (m, 2H), 1.93 (m, 2H), 2.78 (m, 2H), 4.54 (bs, 1H), 5.38 (bs, 1H), 7.02 (d, 1H), 7.28 (dd, 1H), 7.68 (d, 1H), 7.84 (d, 1H), 7.89 (s, 1H), 10.88 (s, 1H), 14.90 (bs, 1H)

[0775] MS (ES-API) m/z 306.1 (M+H.sup.+, 100%).

Example 2

2-Oxo-3-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)indoline-5-carbonitrile

##STR00057##

[0776] 2.1 tert-Butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

[0777] To a solution of 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine (500 mg, 2.97 mmol) in dioxane (7.4 mL) and water (7.4 mL) was added sodium bicarbonate in as a solid in one portion (498 mg, 5.93 mmol). After stirring the resulting suspension for 10 min at RT Boc.sub.2O (777 mg, 3.56 mmol) was added and the mixture was stirred for 16 h. The mixture was diluted with ethyl acetate and the organic layer was washed with water and brine. The organic phase was dried over sodium sulfate, filtered, and evaporated to dryness. Amount 693 mg. Yield 87%.

[0778] .sup.1H-NMR (CDCl.sub.3, 400 MHz) .delta. 1.52 (s, 9H), 2.99 (t, 2H), 3.75 (t, 2H), 4.58 (s, 2H), 7.17 (d, 1H), 7.39 (d, 1H)

[0779] MS (ES-API) m/z 369.1 (M+H.sup.+, 100%).

2.2 tert-Butyl 2-(5-cyano-2-oxoindolin-3-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)carboxyl- ate

##STR00058##

[0781] The title compound was prepared as described for Example 1.2 using 2-oxoindoline-5-carbonitrile (59 mg, 0.373 mmol), X-PHOS (14.23 mg, 0.030 mmol), K.sub.2CO.sub.3 (103 mg, 0.746 mmol), tert-butyl 2-chloro-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (120 mg, 0.448 mmol), and Pd.sub.2(dba).sub.3 (6.83 mg, 7.46 .mu.mol). The mixture was heated in a microwave oven at 100.degree. C. for 2 h min. The mixture was cooled to RT and the resulting precipitate was removed by filtration. The remaining residue was dissolved in a mixture of dichloromethane and 2-propanol and the solution was washed with water. The aqueous layer was re-extracted with dichloromethane/2-propanol (3/1, v/v). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness. Amount 86 mg. Yield 59%.

[0782] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.47 (s, 9H), 2.91 (t, 2H), 3.69 (t, 2H), 4.45 (s, 2H), 7.02 (d, 1H), 7.28 (d, 1H), 7.72 (s, 1H), 7.93 (s, 1H), 10.92 (bs, 1H), 15.05 (bs, 1H)

[0783] MS (ES-API) m/z 391.2 (M+H.sup.+, 100%).

2.3 2-Oxo-3-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)indoline-5-carbonitr- ile

[0784] A solution of tert-butyl 2-(5-cyano-2-oxoindolin-3-yl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxy- late (73 mg, 0.187 mmol) in 4N HCl in dioxane (5 mL) was stirred at RT for 3 h. After this period all volatiles were removed in vacuo. The residue was dissolved in water and washed with ethyl acetate. The aqueous layer was neutralized with saturated solution of sodium bicarbonate and extracted with ethyl acetate. The latter extracts were dried over sodium sulfate, filtered, and evaporated to dryness. Quant. yield.

[0785] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 2.76 (t, 2H), 3.04 (m, 2H), 3.76 (s, 2H), 7.00 (m, 1H), 7.19 (m, 1H), 7.54 (m, 1H), 7.66 (m, 1H), 7.87 (bs, 1H), 10.59 (bs, 1H)

[0786] MS (ES-API) m/z 291.0 (M+H.sup.+, 100%).

Example 3

2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbonitri- le

##STR00059##

[0787] 3.1 7,8-Dihydroquinoline-2,5(1H,6H)-dione

[0788] Methyl propiolate (5.03 ml, 56.2 mmol) was added to finely ground 3-aminocyclohex-2-enone (5 g, 45.0 mmol). The resulting mixture was heated to 105.degree. C. resulting in a dark brown solution and stirred under reflux for 60 min. Then the reflux condenser was removed and the excess methyl propiolate was distilled off by raising the temperature to 170.degree. C. The reaction mixture was cooled to RT and the resulting solid was triturated with dichloromethane (10 mL) and heated to 40.degree. C. for 25 min. The hot mixture was filtered and the yellow residue was washed with dichloromethane (10 mL). The solid was dried under reduced pressure. Amount 2.07 g. Yield 28%.

[0789] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 2.03 (m, 2H), 2.45 (m, 2H), 2.81 (t, 2H), 6.25 (d, 1H), 7.78 (d, 1H), 12.05 (bs, 1H)

[0790] MS (ES-API) m/z 164.1 (M+H.sup.+, 100%).

3.2 2-Chloro-7,8-dihydroquinolin-5(6H)-one

[0791] To a suspension of 7,8-dihydroquinoline-2,5(1H,6H)-dione (1.5 g, 9.19 mmol) in acetonitrile (22 mL) was added dropwise phosphorous oxychloride (1.714 mL, 18.39 mmol). The resulting solution was heated to 100.degree. C. and stirred for 2 h. The reaction was cooled to RT and poured into ice-cold water. After basifying the mixture with 2 M sodium hydroxide solution it was extracted with ethyl acetate (3x). After each extraction the pH of the aqueous phase was checked and if necessary adjusted by adding 1 M sodium hydroxide solution. The combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, cyclohexane/ethyl acetate) yielding a colourless solid. Amount 1.23 g.

[0792] Yield 74%.

[0793] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 2.13 (m, 2H), 2.68 (m, 2H), 3.08 (t, 2H), 7.53 (d, 1H), 8.20 (d, 1H)

[0794] MS (ES-API) m/z 182.0 (M+H.sup.+, 100%).

3.3 2-Hydroxy-3-(5-oxo-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbon- itrile

[0795] To a suspension of 2-chloro-7,8-dihydroquinolin-5(6H)-one (50 mg, 0.275 mmol) and 2-oxoindoline-5-carbonitrile (45.7 mg, 0.289 mmol) in tetrahydrofuran (I.4 mL) was added a 1.0 M solution of sodium bis(trimethylsilyl)amide (641 .mu.L, 0.641 mmol). The mixture was stirred for 3 min at RT and then heated in a microwave oven to 110.degree. C. for 10 min. After cooling to RT the reaction was quenched by addition of methanol (1 mL). The resulting solution was evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol) yielding an orange solid. Amount 17 mg. Yield 20%.

[0796] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 2.17 (m, 2H), 2.59 (t, 2H), 3.08 (t, 2H), 7.06 (d, 1H), 7.38 (dd, 1H), 7.68 (d, 1H), 7.98 (m, 2H), 11.11 (s, 1H), 14.78 (bs, 1H)

[0797] MS (ES-API) m/z 304 (M+H.sup.+, 100%).

Example 4

2-Hydroxy-3-(8-hydroxy-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-carbon- itrile

##STR00060##

[0798] 4.1 2-Chloro-8-hydroxy-5,6,7,8-tetrahydroquinoline 1-oxide

[0799] To an ice-cold solution of 2-chloro-5,6,7,8-tetrahydroquinolin-8-ol (300 mg, 1.634 mmol) in dichloromethane (5 mL) was added 3-chloroperbenzoic acid (604 mg, 2.451 mmol) in small portions over a period of 5 min. The reaction mixture was slowly warmed to RT and stirred for 20 h. The reaction was quenched by the addition of water. The aqueous phase was removed and the organic layer was washed with a 10% aqueous sodium thiosulfate solution (2x), with a 2M sodium carbonate solution (2x), and with brine (1x). The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness furnishing a beige solid. Amount 320 mg. Yield 98%.

[0800] .sup.1H-NMR (CDCl.sub.3, 400 MHz) .delta. 1.80 (m, 1H), 1.93 (m, 1H), 2.13 (m, 2H), 2.72 (m, 1H), 2.84 (m, 1H), 5.13 (t, 1H), 7.09 (d, 1H), 7.40 (d, 1H)

[0801] MS (ES-API) m/z 200.1 (M+H.sup.+, 100%).

4.2 2-(5-Cyano-2-oxoindolin-3-yl)-8-hydroxy-5,6,7,8-tetrahydroquinoline 1-oxide

[0802] The title compound was prepared as described for Example 3.3 using 2-chloro-8-hydroxy-5,6,7,8-tetrahydroquinoline 1-oxide (100 mg, 0.501 mmol), 2-oxoindoline-5-carbonitrile (83 mg, 0.526 mmol), tetrahydrofuran (2.5 mL), and a 1.0 M solution of sodium bis(trimethylsilyl)amide (1.668 .mu.L, 1.668 mmol). The reaction was quenched by addition of methanol (2.5 mL). The resulting solution was evaporated to dryness. The crude was used in the following reaction step without further purification.

[0803] MS (ES-API) m/z 322.1 (M+H.sup.+, 100%).

4.3 2-Hydroxy-3-(8-hydroxy-5,6,7,8-tetrahydroquinolin-2-yl)-1H-indole-5-ca- rbonitrile

[0804] To a suspension of crude 2-(5-cyano-2-oxoindolin-3-yl)-8-hydroxy-5,6,7,8-tetrahydroquinoline 1-oxide (263 mg, 0.819 mmol) in ethyl acetate (12 mL) and acetonitrile (12 mL) was added dropwise a solution of phosphorous trichloride (0.644 mL, 7.37 mmol) in ethyl acetate (4 mL). The resulting suspension was stirred at RT. After 24 h the mixture was diluted with ethyl acetate and washed with a saturated sodium bicarbonate solution (2x). The aqueous phase was re-extracted with ethyl acetate (1x) and the combined organic extracts were dried over sodium sulfate, filtered, and evaporated to dryness (52 mg). The crude was dissolved in a mixture of water (2 mL) and dimethylformamide (3 mL) and the solution was heated in a microwave oven at 120.degree. C. for 5 min. After cooling to RT the reaction mixture was diluted with ethyl acetate was washed with brine (5x). The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol) yielding yellow solid. Amount 8.6 mg. Yield 18%.

[0805] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.70 (m, 2H), 1.90 (m, 1H), 2.10 (m, 1H), 2.63 (m, 2H), 4.66 (m, 1H), 6.04 (d, 1H), 6.98 (d, 1H), 7.24 (d, 1H), 7.61 (d, 1H), 7.70 (d, 1H), 7.88 (s, 1H), 10.81 (s, 1H), 15.05 (bs, 1H)

[0806] MS (ES-API) m/z 306.0 (M+H.sup.+, 100%).

Example 5

3-(6,7-Dihydro-5H-pyrrolo[3,4-b]pyridin-2-yl)-2-oxoindoline-5-carbonitrile hydrochloride

##STR00061##

[0807] 5.1 tert-Butyl 2-chloro-5H-pyrrolo[3,4-b]pyridine-6(7H)-carboxylate

[0808] The title compound was prepared as described for Example 2.1 using 2-chloro-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine (500 mg, 3.23 mmol), sodium bicarbonate (543 mg, 6.47 mmol), and Boc2O (870 mg, 3.987 mmol) in a mixture of dioxane (7.4 mL) and water (7.4 mL). After work up as described in Example 4 the titled compound was obtained as a beige solid. Amount 814 mg. Yield 99%.

[0809] .sup.1H-NMR (CDCl.sub.3, 400 MHz) .delta. 1.55 (s, 9H), 4.69 (m, 4H), 7.26 (d, 1H), 7.54 (m, 1H); MS (ES-API) m/z 255.1 (M+H.sup.+, 10%).

5.2 tert-Butyl 2-(5-cyano-2-oxoindolin-3-yl)-5H-pyrrolo[3,4-b]pyridine-6(7H)carboxylate

##STR00062##

[0811] The title compound was prepared as described for Example 1.2 using 2-oxoindoline-5-carbonitrile (200 mg, 1.265 mmol), tert-butyl 2-chloro-5H-pyrrolo[3,4-b]pyridine-6(7H)carboxylate (387 mg, 1.517 mmol), K.sub.2CO.sub.3 (350 mg, 2.53 mmol), X-PHOS (48.2 mg, 0.101 mmol), Pd.sub.2(dba).sub.3 (23.16 mg, 0.025 mmol), and tetrahydrofuran (4 mL). The reaction mixture was heated in a microwave oven at 100.degree. C. for 90 min. After cooling to RT the mixture was filtered and the yellow residue was washed with tetrahydrofuran (10 mL) and water (10 mL). The solid was dried under reduced pressure. Amount 193 mg. Yield 40%.

[0812] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.47 (s, 9H), 4.52 (m, 2H), 4.72 (d, 2H), 7.04 (d, 1H), 7.28 (d, 1H), 7.80 (m, 2H), 7.98 (s, 1H), 11.05 (s, 1H)

[0813] MS (ES-API) m/z 377.1 (M+H.sup.+, 10%).

5.3 3-(6,7-Dihydro-5H-pyrrolo[3,4-b]pyridin-2-yl)-2-oxoindoline-5-carbonit- rile hydrochloride

[0814] To a suspension of tert-butyl 2-(5-cyano-2-oxoindolin-3-yl)-5H-pyrrolo[3,4-b]pyridine-6(7H)-carboxylate (70 mg, 0.186 mmol) in dioxane (2 mL) was added dropwise 4N HCl in dioxane (2.5 mL). After stirring the resulting mixture at RT for 3 d all volatiles were removed under reduced pressure. The residue was suspended in diethylether and stirred at RT for 2 h. The suspension was filtered, the remaining solid was washed with diethylether and dried under reduced pressure. Amount 55 mg. Yield 95%.

[0815] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 4.48 (m, 2H), 4.67 (s, 2H), 7.09 (m, 1H), 7.40 (m, 1H), 7.85 (m, 2H), 8.12 (s, 1H), 9.87 (m, 2H), 11.18 (m, 1H)

[0816] MS (ES-API) m/z 277.1 (M+H.sup.+, 100%).

Example 6

3-(5-Methoxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonitrile

##STR00063##

[0817] 6.1 2-Chloro-5-methoxy-5,6,7,8-tetrahydroquinoline

[0818] To a solution of 2-chloro-5,6,7,8-tetrahydroquinolin-5-ol (319 mg, 1.737 mmol) in tetrahydrofuran (8 mL) was added in small portions sodium hydride (83 mg, 2.085 mmol; 60 on mineral oil). After stirring the resulting suspension for 20 min at RT methyl iodide (0.119 ml, 1.911 mmol) was added dropwise. The reaction mixture was stirred at RT for 20 h. The reaction was quenched by addition of a saturated ammonium chloride solution. The layers were separated and the aqueous layer was extracted with ethyl acetate (3x). The combined organic layers were washed with brine and dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, cyclohexane/ethylacetate) yielding a slightly yellow oil. Amount 210 mg. Yield 61%.

[0819] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.77 (m, 1H), 1.90 (m, 3H), 2.79 (m, 2H), 3.37 (s, 3H), 4.37 (m, 1H), 7.32 (d, 1H), 7.77 (d, 1H)

[0820] MS (ES-API) m/z 198.1 (M+H.sup.+, 100%).

6.2 3-(5-Methoxy-5,6,7,8-tetrahydroquinolin-2-yl)-2-oxoindoline-5-carbonit- rile

[0821] The title compound was prepared as described for Example 1.2 using 2-oxoindoline-5-carbonitrile (60 mg, 0.379 mmol), 2-chloro-5-methoxy-5,6,7,8-tetrahydroquinoline (90 mg, 0,455 mmol), K.sub.2CO.sub.3 (105 mg, 0.76 mmol), X-PHOS (14.47 mg, 0.030 mmol), Pd.sub.2(dba).sub.3 (6.95 mg, 7.59 .mu.mol), and tetrahydrofuran (1.9 mL). The reaction mixture was heated in a microwave oven at 100.degree. C. for 120 min. After cooling to RT the mixture was diluted with ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2x). The combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness. The crude was purified by flash chromatography (silica gel, dichloromethane/methanol). The product containing fractions were combined, evaporated to dryness, and the resulting solid was triturated with diethylether. Amount 27 mg. Yield 22%.

[0822] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) .delta. 1.87 (m, 4H), 2.81 (m, 2H), 3.40 (s, 3H), 4.28 (s, 1H), 7.04 (d, 1H), 7.31 (d, 1H), 7.68 (d, 1H), 7.77 (d, 1H), 7.91 (s, 1H), 10.96 (s, 1H), 14.93 (bs, 1H)

[0823] MS (ES-API) m/z 320.1 (M+H.sup.+, 100%).

II. Biological Tests

[0824] The compounds according to the invention exhibit very good affinities for GSK-3 (<1 .mu.M, frequently <100 nM) and exhibited good selectivity against multiple kinase targets.

[0825] Methods--Biochemical hGSK-3Beta Assay

[0826] Compounds were tested for their ability to inhibit human Glycogen Synthase Kinase-3 beta (hGSK-3p) to phosphorylate biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE. Compounds were incubated with 0.5 .mu.Ci 33P-ATP, 10 .mu.M ATP, 0.0125U hGSK-3.beta. (Upstate cell signaling solutions) and 1 .mu.M substrate (biotin-YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE) in 50 mM HEPES, 10 mM MgCl.sub.2, 100 mM Na.sub.3VO.sub.4, 1 mM DTT, 0.0075% Triton, 2% DMSO (total volume 50 .mu.L) for 30 minutes at room temperature. The incubation was stopped by addition of an equal volume of 100 mM EDTA, 4M NaCl. 80 .mu.L of this mixture was added to streptavidin-coated Flashplates (PerkinElmer). Following a wash step, 33P incorporation was quantified on a MicroBeta microplate liquid scintillation counter (Perkin Elmer). IC.sub.50s were determined by fitting a sigmoidal dose-response curve to the counts obtained at the different concentrations in GraphPad Prism.

[0827] The results of the binding tests are given in the table below.

TABLE-US-00002 Example # GSK-3.beta. IC.sub.50 (nM) 1 +++ 2.2 +++ 2 +++ 3 +++ 4 +++ 5 +++ 6 +++ n.d. not determined GSK-3.beta. IC.sub.50 (nM): Ranges: + >10 .mu.M ++ from 100 nM to 10 .mu.M +++ <100 nM

Claims

1. A heterocyclic compound of the general formulae IA and IB ##STR00064## a stereoisomer, N-oxide, tautomer and/or physiologically tolerated acid addition salt thereof; and the compound of the general formulae IA and IB, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, wherein X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are independently of each other selected from the group consisting of CR.sup.1 and N; each R.sup.1 is independently selected from the group consisting of hydrogen, cyano, NR.sup.aR.sup.b, OH, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, formyl, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, COOH, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, C.sub.1-C.sub.6-alkyl-NR.sup.aR.sup.b, CO--NR.sup.aR.sup.b, an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising 1, 2 or 3 heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R.sup.7 and wherein Ar may also be bonded via a CH.sub.2 group, and saturated or partially unsaturated 3-, 4-, 5-, 6- or 7-membered heterocyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein the heterocyclic radical is unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; R.sup.2 is hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-haloalkenyl, OH or F; R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1, 2 or 3 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O, S, SO, SO.sub.2, NR.sup.c and NO, and where 1, 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8; where the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are independently selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy and NR.sup.aR.sup.b; each R.sup.7 is independently selected from the group consisting of halogen, OH, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, CO--NR.sup.aR.sup.b, a phenyl group and a saturated, partially unsaturated or aromatic 5- or 6-membered heterocyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein phenyl and the hetero-cyclic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, or in the hetero-cyclic ring two geminally bound radicals may together form a group .dbd.O; each R.sup.8 is independently selected from the group consisting of halogen, OH, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-halocycloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.1-C.sub.6-haloalkoxycarbonyl, CO--NR.sup.aR.sup.b, a phenyl group and a saturated, partially unsaturated or aromatic 3-, 4-, 5-, 6- or 7-membered heterocyclic radical comprising 1, 2 or 3 heteroatoms selected from O, S and N as ring members, wherein phenyl and the heterocyclic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals independently selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; R.sup.a and R.sup.b are independently of each other selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl; or R.sup.a and R.sup.b form, together with the nitrogen atom to which they are bonded, a 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom-containing group selected from N, O, S, SO and SO.sub.2 as a ring member, where the N-heterocyclic ring may carry 1 or 2 radicals selected from halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy; and each R.sup.c is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.4-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl.

2. The heterocyclic compound of claim 1, wherein R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1, 2 or 3 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, O, S, SO, SO.sub.2, NR.sup.c and NO, and where 1, 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8; with the proviso that in case R.sup.3 and R.sup.4 form together a bridging group --(CH.sub.2).sub.m--, the CH.sub.2 unit bound in the position of R.sup.3 is not replaced by a NW group; where the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are independently selected from the group consisting of hydrogen, halogen, cyano, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy, and where R.sup.4, R.sup.5 and R.sup.6 may independently also be selected from NR.sup.aR.sup.b.

3. The heterocyclic compound of claim 1, wherein R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5; or R.sup.5 and R.sup.6 form together a bridging group --(CH.sub.2).sub.m--, wherein m is 3, 4 or 5, where 1 or 2 of the CH.sub.2 groups may be replaced by a group or a heteroatom selected from CO, 0 and NW, and where 1 or 2 or 3 hydrogen atoms of the bridging group may be replaced by a radical R.sup.8.

4. The heterocyclic compound of claim 1, where m is 3 or 4.

5. The heterocyclic compound of claim 3, where the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2O--, --CH.sub.2OCH.sub.2--, --NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.c--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2O--, --NR.sup.cCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2NR.sup.c--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8.

6. The heterocyclic compound of claim 5, where the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2O--, --CH.sub.2OCH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --OCH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2OCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2OCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2O--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8.

7. The heterocyclic compound of claim 6, where the bridging group is selected from --CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2NR.sup.cCH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2NR.sup.cCH.sub.2--, --C(.dbd.O)CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2C(.dbd.O)CH.sub.2-- and --CH.sub.2CH.sub.2CH.sub.2C(.dbd.O)--, where the hydrogen atoms of the above groups may be replaced by 1 or 2 radicals R.sup.8.

8. The heterocyclic compound of claim 1, where the radicals R.sup.3, R.sup.4, R.sup.5 and R.sup.6, which are not part of the bridging group, are hydrogen.

9. The heterocyclic compounds of claim 1, where R.sup.3 and R.sup.4; or R.sup.4 and R.sup.5 form together a bridging group.

10. The heterocyclic compounds of claim 9, where R.sup.3 and R.sup.4 form together a bridging group.

11. The heterocyclic compound of claim 1, where each R.sup.8 is independently selected from the group consisting of halogen, OH, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, NR.sup.aR.sup.b, C.sub.1-C.sub.6-alkylcarbonyl, C.sub.1-C.sub.6-haloalkylcarbonyl, C.sub.1-C.sub.6-alkoxycarbonyl and C.sub.1-C.sub.6-haloalkoxycarbonyl.

12. The heterocyclic compound of claim 11, where each R.sup.8 is independently selected from the group consisting of OH, C.sub.1-C.sub.4-alkoxy and C.sub.1-C.sub.4-haloalkoxy.

13. The heterocyclic compound of claim 1, where R' is hydrogen or C.sub.1-C.sub.6-alkoxycarbonyl.

14. The heterocyclic compound of claim 1, where all of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are CR.sup.1 or one of X.sup.2, X.sup.3 and X.sup.4 is N and the others are CR.sup.1.

15. The heterocyclic compound of claim 14, where all of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 are CR.sup.1.

16. The heterocyclic compound of claim 15, where X.sup.1, X.sup.2 and X.sup.4 are CH and X.sup.3 is CR.sup.1.

17. The heterocyclic compound of claim 16, where X.sup.3 is CR.sup.1, wherein R.sup.1 is H, CN or COOH, preferably CN.

18. The heterocyclic compound of claim 1, where R.sup.2 is hydrogen.

19. The heterocyclic compound of claim 1, where R.sup.2 is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-fluoroalkyl, C.sub.2-C.sub.4-alkenyl or fluorine.

20. (canceled)

21. (canceled)

22. A pharmaceutical composition comprising at least one heterocyclic compound as defined in claim 1, a stereoisomer, N-oxide, tautomer and/or physiologically tolerated acid addition salt thereof or comprising at least one heterocyclic compound as defined in any of the preceding claims wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, and at least one physiologically acceptable carrier and/or auxiliary substance.

23. (canceled)

24. (canceled)

25. (canceled)

26. (canceled)