Aryl and hetaryl amides as modulators of EP2 receptors

摘要

The aryl or hetarylamide derivative is new. The aryl or hetarylamide derivative of general formula (I), its isomer, diastereomer, enantiomer, salt or cyclodextrin clathrate, is new. A : aryl, preferably phenyl or naphthyl or hetero aryl residue, which is substituted with one or multiple R 3>or R 4>as per requirement; R 1>H, 1-6C alkyl residue, which is substituted as per requirement; R 2>H, halogen, cyano, 1-4C-alkoxy residue or 1-6C-alkyl, -S(O) q-CH 3, where q=0-2; R 3>H, halogen, amino, -S(O) p-C 1-C 6-alkylgroup, where p=0-2, 1-6C-acyl, NH-CO-NH 2, -O-CO-NH(C 1-C 6-alkyl), -O-CO-N(C 1-C 6-alkyl) 2, NH-CO-C 1-C 6-alkylresidue, 1-6C-alkyl, which is subtituted with one or multiple 1-6C-acyl, alkoxy, hydroxy, cyano, CO 2-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, 5-12C-heteroaryl, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl) or CO-N(C 1-C 6-alkyl) 2, 1-6C-alkoxy, which is subtituted with one or multiple hydroxy, cyano, CO 2-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, NH-C 3-C 6cycloalkyl, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl) or CO-N(C 1-C 6-alkyl) 2, O-C 6-C 12-aryl, CH 2O-C 6-C 12-aryl or O-C 5-C 16 heteroaryl, which is subtituted with hydroxy, cyano, COOH or CO-NH 2as per requirement, hydroxy, cyano, O-CO-(C 1-C 6-alkyl), CO-NH(C 5-C 12-heteroaryl), NH-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, 6-12C-aryl, which is subtituted with one or multiple halogen atoms, 1-6C-alkyl, 3-6C-cycloalkyl, 1-6C-acyl, 1-6C-alkoxy, 6-12C-aryl, 5-12C-heteroaryl, hydroxy, CH 2-OH, cyano, CH 2-CN, amino, CO 2-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, NHSO 2CH 3, SO 2NH 2, SO 2NH(C 1-C 6-alkyl), SO 2N(C 1-C 6-alkyl) 2, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl), CO-N(C 1-C 6-alkyl) 2, CO-NH(C 5-C 12-heteroaryl), NHCO(C 1-C 6-alkyl), CH 2-NH-CO(C 1-C 6-alkyl), NH-CO(C 5-C 12-heteroaryl), CH 2-NH-CO(C 5-C 12-heteroaryl), styryl or -S(O) r-CH 3, where r=0-2 or is subtituted with -O-CH 2-O- or -O-C(CH 3) 2-O- at two neighbouring positions, monocyclic 5-7C-heteroaryl, which is subtituted with one or multiple halogen atoms, CF 3, 1-6C-acyl, 1-6C-alkoxy, hydroxy, CH 2-OH, cyano, CO 2-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl) or CO-N(C 1-C 6-alkyl) 2, bi- or tricyclic 8-12C-heteroaryl, which is subtituted with one or multiple halogen atoms, 1-6C-alkyl, acyl, alkoxy, hydroxy, cyano, CO 2-(C 1-C 6-alkyl), N-(C 1-C 6-alkyl) 2, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl) or CO-N(C 1-C 6-alkyl) 2, O-CO-S-, -S-CO-O-, CH2-CO-O-, O-CO-CH2-, -CH2-CO-NH-, -NH-CO-CH2-, -O-CO-NH, -NH-CO-O-, -CO-CH 2-(CH 2) m, -CH 2-(CH 2) m-CO-, -O-(CH 2) m-O-, -O-C-(CH 3) 2-O- or -CH 2-(CH 2) m-CH 2-, where m=1-3, or 3-6C-cycloalkyl, which is subtituted with one or multiple halogen atoms, 1-6C-alkyl, hydroxy, cyano, CO 2-(C 1-C 6-alkyl), C 1-C 6-acyl, N-(C 1-C 6-alkyl) 2, COOH, CO-NH 2, CO-NH(C 1-C 6-alkyl), CO-N(C 1-C 6-alkyl) 2or 1-6C-alkoxy; R 4>same as variable group R 3>; and Y' : -(CH 2) n-, where n=1-3. Provided that: (A) when R 2>=cyano or R 1>,R 2>=1-6C-akyl residue, where one residue is simply substituted and R 4>=1-6C-acyl, -O-CO-NH(C 1-C 6-alkyl), -O-CO-N(C 1-C 6-alkyl) 2, C 6-C 12-aryloxy, 5-16C-heteroaryloxy, hydroxy, cyano, N-(C 1-C 6-alkyl) 2or -S(O) p-C 1-C 6-alkyl, where p=0-2, then R 3>=monocyclic 5-7C-heteroaryl, which is subtituted with one or multiple 1-6C-alkyl; and (B) when R 2>=cyano or R 1>,R 2>=1-6C-akyl residue, where one residue is simply substituted, then R 4>=monocyclic 5-7C-heteroaryl, which is subtituted with one or multiple 1-6C-alkyl. [Image] ACTIVITY : Gynecological; Analgesic; Contraceptive; Osteopathic; Cytostatic. MECHANISM OF ACTION : E-prostanoid 2 (EP 2) receptor antagonist. Test details are described but no results for the compounds of the claims are given.