AZOLOARINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICALS CONTAINING THESE COMPOUNDS AND THE USE THEREOF
The invention relates to azoloarine derivatives of formula I wherein R, A, B, D, Y, X, M and W are as defined herein, and their physiologically tolerated salts.
1 . A compound of formula I,
wherein:
M is R1-N(R2)-C(═O)—, R5-C(═O)—N(R1)-, R5-S(O) 0-2 —N(R1)-, or R1-N(R2)-S(O) 0-2 —;
W is O, CH 2 , or C═O;
X is N—R4, O, or S;
A, B, D and Y are independently of one another C(R3) or N, provided that a maximum of two of the radicals A, B, D, Y are N;
R is (C 1 -C 16 )-alkyl, (C 1 -C 5 )-alkyloxy, (C 1 -C 5 )-alkylthio, amino, (C 1 -C 5 )-alkylamino, di-(C 2 -C 8 )-alkylamino, (C 1 -C 6 )-alkylcarbonylamino, (C 1 -C 6 )-alkoxycarbonylamino, halogen, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl;
R1 is (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino,
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C m )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
—(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, Wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl; or
R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring system may be replaced by one to three atoms or atomic groups from the group of —CHR4-, —CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —;
R3 is hydrogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, cyano, (C 1 -C 6 )-alkylcarbonyl, halogen, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl, or aminosulfonyl;
R4 is hydrogen, or (C 1 -C 5 )-alkyl; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or (C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
—(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
2 . The compound according to claim 1 , wherein
W is O or C═O;
X is N—R4;
R1 (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl;
or R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the group of —CHR4-, —CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
3 . The compound according to claim 1 , wherein
M is R1-N(R2)-C(═O)— or R5-C(═O)—N(R1)-;
W is O or C═O;
X is NH;
A, B, D and Y are CH;
R1 is (C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
4 . The compound according to claim 1 , wherein
M is R1-NH—C(═O)—;
W is O or C═O;
X is NH;
A, B, D and Y are CH;
R1 is (C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof
5 . The compound according to claim 1 , wherein
M is R1-NH—C(═O)—;
W is O or C═O;
X is NH;
A, B, D and Y are CH;
R1 is —(CH 2 ), —(C 6 -C 10 )-aryl, —(CH 2 ) n —(C 3 -C 12 )-heteroaryl, —(CH 2 ), —(C 3 -C 12 )-heterocyclyl or —(CH 2 ) n —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl rings is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino; and
n is 1, 2, 3 or 4;
or a physiologically tolerated salt thereof.
6 . The compound according to claim 1 , which is:
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-pyridin-3-ylpropyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-phenylpropyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-phenethylcarboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-methylbutyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(2-cyclopropylethyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-cyclopropylmethylcarboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(5-chlorothiophen-2-ylmethyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(thiazol-2-ylmethyl)carboxamide;
2-(4-Phenoxyphenyl)-3H-benzimidazole-5-(3-butoxypropyl)carboxamide;
2-[4-(2-Chlorophenoxy)phenyl]-3H-benzoimidazole-5-phenethylcarboxamide;
2-[4-(2-Chlorophenoxy)phenyl]-3H-benzoimidazole-5-(3-methylbutyl)carboxamide;
2-[4-(2-Chlorophenoxy)phenyl]-3H-benzoimidazole-5-(2-cyclopropylethyl)carboxamide;
2-[4-(2-Chlorophenoxy)phenyl]-3H-benzoimidazole-5-(5-chlorothiophen-2-yl-methyl)carboxamide;
2-[4-(2-Chlorophenoxy)phenyl]-3H-benzoimidazole-5-(thiazol-2-ylmethyl)carboxamide;
2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(5-chlorothiophen-2-ylmethyl)-carboxamide;
2-[4-(2-Trifluoromethylbenzoyl)phenyl]-3H-benzimidazole-5-(thiophen-2-ylmethyl)-carboxamide;
2-[4-(2-Trifluoromethylbenzoyl)phenyl]-3H-benzoimidazole-5-isobutylcarboxamide;
2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(2-cyclopropylethyl)-carboxamide;
2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(3-methylbutyl)carboxamide;
2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(thiazol-2-ylmethyl)carboxamide;
2-[4-(2-Trifluoromethylphenoxy)phenyl]-3H-benzimidazole-5-(3-phenylpropyl)carboxamide;
2-[4-(2-Trifluoromethylbenzoyl)phenyl]-3H-benzimidazole-5-(5-chlorothiophen-2-ylmethyl)-carboxamide; or
2-[4-(2-Trifluoromethylbenzoyl)phenyl]-1H-benzimidazole-5-(thiazol-2-ylmethyl)-carboxamide;
or a physiologically tolerated salt thereof.
7 . A pharmaceutical composition comprising the compound according to claim 1 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
8 . The pharmaceutical composition according to claim 6 , further comprising one or more active ingredients selected from the group consisting of antidiabetics, hypoglycemic active ingredients, HMGCoA reductase inhibitors, cholesterol absorption inhibitors, PPAR gamma agonists, PPAR alpha agonists, PPAR alpha/gamma agonists, PPAR delta agonists, fibrates, MTP inhibitors, bile acid absorption inhibitors, MTP inhibitors, CETP inhibitors, polymeric bile acid adsorbents, LDL receptor inducers, ACAT inhibitors, antioxidants, lipoprotein lipase inhibitors, ATP-citrate lyase inhibitors, squalene synthetase inhibitors, lipoprotein(a) antagonists, HM74A receptor agonists, lipase inhibitors, insulins, sulfonylureas, biguanides, meglitinides, thiazolidinediones, α-glucosidase inhibitors, active ingredients which act on the ATP-dependent potassium channel of the beta cells, glycogen phosphorylase inhibitors, glucagon receptor antagonists, activators of glucokinase, inhibitors of gluconeogenesis, inhibitors of fructose-1,6-bisphosphatase, modulators of glucose transporter 4, inhibitors of glutamine-fructose-6-phosphate amidotransferase, inhibitors of dipeptidylpeptidase IV, inhibitors of 11-beta-hydroxysteroid dehydrogenase 1, inhibitors of protein tyrosine phosphatase 1B, modulators of the sodium-dependent glucose transporter 1 or 2, modulators of GPR40, inhibitors of hormone-sensitive lipase, inhibitors of acetyl-CoA carboxylase, inhibitors of phosphoenolpyruvate carboxykinase, inhibitors of glycogen synthase kinase-3 beta, inhibitors of protein kinase C beta, endothelin-A receptor antagonists, inhibitors of I kappaB kinase, modulators of the glucocorticoid receptor, CART agonists, NPY agonists, MC4 agonists, orexin agonists, H3 agonists, TNF agonists, CRF agonists, CRF BP antagonists, urocortin agonists, β3 agonists, CB1 receptor antagonists, melanocyte-stimulating hormone agonists, CCK agonists, serotonin reuptake inhibitors, mixed serotoninergic and noradrenergic compounds, 5HT agonists, bombesin agonists, galanin antagonists, growth hormones, growth hormone-releasing compounds, TRH agonists, uncoupling protein 2 or 3 modulators, leptin agonists, DA agonists, bromocriptine, Doprexin, lipase/amylase inhibitors, PPAR modulators, RXR modulators, TR-β agonists and amphetamines.
9 . A pharmaceutical composition comprising the compound according to claim 2 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
10 . A pharmaceutical composition comprising the compound according to claim 3 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
11 . A pharmaceutical composition comprising the compound according to claim 4 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
12 . A pharmaceutical composition comprising the compound according to claim 5 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
13 . A pharmaceutical composition comprising the compound according to claim 6 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient.
14 . A method for treating obesity, diabetes, metabolic syndrome, insulin resistance cardiovascular disorder, CNS disorder, schizophrenia, Alzheimer's disease, or for lowering lipid level, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a physiologically tolerated salt thereof.
15 . A process for preparing a pharmaceutical composition comprising the compound according to claim 1 or a physiologically tolerated salt thereof, in combination with a pharmacologically acceptable carrier or excipient, comprising mixing the compound according to claim 1 or the physiologically compatible salt thereof with the pharmacologically acceptable carrier or excipient, and converting the mixture into to a form suitable for administration.
16 . A method for treating obesity, diabetes, metabolic syndrome, insulin resistance cardiovascular disorder, CNS disorder, schizophrenia, Alzheimer's disease, or for lowering lipid level, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a compound of formula I
wherein:
M is R1-N(R2)-C(═O)—, R5-C(═O)—N(R1)-, R5-S(O) 0-2 —N(R1)-, R1-N(R2)-S(O) 0-2 —, or a heterocycle which may comprise 2 to 4 heteroatoms from the group of N, O and S, wherein the heterocycle is optionally substituted by (C 1 -C 16 )-alkyl, or doubly bonded oxygen;
W is O, CH 2 or C═O;
X is N—R4, O or S;
A, B, D and Y are independently of one another C(R3) or N, provided that a maximum of two of the radicals A, B, D, Y are N;
R is hydrogen, (C 1 -C 16 )-alkyl, (C 1 -C 5 )-alkyloxy, (C 1 -C 5 )-alkylthio, amino, (C 1 -C 5 )-alkylamino, di-(C 2 -C 8 )-alkylamino, (C 1 -C 6 )-alkylcarbonylamino, (C 1 -C 6 )-alkoxycarbonylamino, halogen, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl;
R1 is (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino,
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
—(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl;
or R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring system may be replaced by one to three atoms or atomic groups from the group of —CHR4-, —CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —;
R3 is hydrogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, cyano, (C 1 -C 6 )-alkylcarbonyl, halogen, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl, or aminosulfonyl;
R4 is hydrogen or (C 1 -C 5 )-alkyl; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
—(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
17 . The method according to claim 16 , wherein:
W is O or C═O;
X is N—R4;
R1 is (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl;
or R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the group of —CHR4-, —CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino,
wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
18 . The method according to claim 16 , wherein:
M is R1-N(R2)-C(═O)— or R5-C(═O)—N(R1)-;
W is O or C═O;
X is N—R4;
R1 is (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl may optionally be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino;
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl;
or R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the group of —CHR4-, —CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.
19 . The method according to claim 17 , wherein:
M is R1-N(R2)-C(═O)— or R5-C(═O)—N(R1)-;
W is O or C═O;
X is N—R4;
A, B, D and Y are CH;
R1 is (C 2 -C 10 )-alkyl, which is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or (C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, or
(C 1 -C 10 )-alkyl, which is substituted by —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
R2 is hydrogen, (C 2 -C 16 )-alkyl, —(C 6 -C 10 )-aryl, or (C 1 -C 4 )-alkylene-(C 6 -C 10 )-aryl;
or R1 and R2 taken together with the nitrogen atom to which they are attached form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the group of —CHR4-CR4R5-, —(C═R4)-, —NR6-, —C(═O)—, —O—, —S—, —SO— and —SO 2 —;
R4 is hydrogen; and
R5 is hydrogen, (C 1 -C 16 )-alkyl, amino, (C 1 -C 16 )-alkylamino, or di-(C 2 -C 12 )-alkylamino, wherein the alkyl is optionally substituted by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, —(C 6 -C 10 )-aryl, —(C 3 -C 12 )-heteroaryl, —(C 3 -C 12 )-heterocyclyl or —(C 3 -C 12 )-cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl or cycloalkyl is optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, or di-(C 2 -C 12 )-alkylamino;
or a physiologically tolerated salt thereof.