Patent EP-2003119-A1 (EP)
Inventor: BUCHMANN BERND
IPC: A61K31/517
Filed: 2007-06-13
Abstract: 7-Fluoro-1H-indole compounds (I) and their isomers, diastereomers, enantiomers or salts and/or cyclodextrin clathrates, are new. 7-Fluoro-1H-indole compounds of formula (I) and their isomers, diastereomers, enantiomers or salts and/or cyclodextrin clathrates, are new. A : 6-12C-aryl or 5-16C-heteroaryl (optionally substituted by one or more R 4>and/or R 3>); R 1>H or optionally substituted 1-6C-alkyl; R 2>H, halo, CN, S(O) q-CH 3, 1-4C-alkoxy or 1-6C-alkyl (optionally substituted); either R 3>H, halo, amino, S(O) p-1-6C-alkyl, SO 2NH 2, COOH, CO-NH 2, NH-CO-NH 2, 1-6C-acyl, O-CO-NH(1-6C-alkyl), O-CO-N(1-6C-alkyl) 2or NH-CO-1-6C-alkyl, 1-6C-alkyl (optionally substituted by one or more 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, COOH, CONH 2, CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2), 1-6C-alkoxy (optionally substituted by one or more OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, COOH, CONH2, CONH(1-6C-alkyl) or CO-N(1-6C-alkyl) 2), O-6-12C-aryl, CH 2-O-6-12C-aryl, O-5-16C-heteroaryl, OH, CN, CO 2-(1-6C-alkyl), OCO- (1-6C-alkyl), N-(1-6C-alkyl) 2, NH-(1-6C-alkyl), CO-NH(5-12C-heteroaryl), CO-NH(1-6C-alkyl), CON(1-6C-alkyl) 2, 6-12C-aryl (optionally substituted by one or more halo, 1-6C-alkyl, 3-6C-cycloalkyl, 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N(1-6C-alkyl) 2, CONH(1-6C-alkyl) or CON(1-6C-alkyl) 2), 5-12C-heteroaryl (optionally substituted by one or more halo, 1-6C-alkyl, 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, CONH(1-6C-alkyl) or CON(1-6C-alkyl) 2) or 3-6C-cycloalkyl (optionally substituted by one or more halo, 1-6C-alkyl, OH, CN, CO 2-(1-6C-alkyl), 1-6C-acyl, N-(1-6C-alkyl) 2, CONH(1-6C-alkyl), CON(1-6C-alkyl) 2or 1-6C-alkoxy); and R 4>H, halo, amino, S(O) p-1-6C-alkyl, SO 2NH 2, COOH, CONH 2, NHCONH 2, 1-6C-acyl, NH-CO-1-6C-alkyl, O-CO-NH(1-6C-alkyl), OCO-N(1-6C-alkyl) 2, 1-6C-alkyl (optionally substituted by one or more 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, COOH, CONH 2, CO-NH(1-6C-alkyl) or CON(1-6C-alkyl) 2), 1-6C-alkoxy (optionally substituted by one or more OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, COOH, CONH 2, CONH(1-6C-alkyl) or CON(1-6C-alkyl) 2), O-6-12C-aryl, CH 2-O-6-12C-aryl, O-5-16C-heteroaryl, OH, CN, CO 2(1-6C-alkyl), OCO(1-6C-alkyl), N(1-6C-alkyl) 2, NH(1-6C-alkyl), CONH(5-12C-heteroaryl), CONH(1-6C-alkyl), CON(1-6C-alkyl) 2, 6-12C-aryl (optionally substituted by one or more halo, 1-6C-alkyl, 3-6C-cycloalkyl, 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, CONH(1-6C-alkyl) or CO-N(1-6C-alkyl) 2), 5-12C-heteroaryl (optionally substituted by one or more halo, 1-6C-alkyl, 1-6C-acyl, 1-6C-alkoxy, OH, CN, CO 2-(1-6C-alkyl), N-(1-6C-alkyl) 2, CONH(1-6C-alkyl) or CO-N(1-6C-alkyl) 2) or 3-6C-cycloalkyl (optionally substituted by one or more halo, 1-6C-alkyl, OH, CN, CO 2-(1-6C-alkyl), 1-6C-acyl, N-(1-6C-alkyl) 2, CONH(1-6C-alkyl), CON(1-6C-alkyl) 2or 1-6C-alkoxy); or R 3>R 4>in o-, m- or p- position : O-CO-S, S-CO-O, CH 2-CO-O-, O-CO-CH 2, 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; X : O, S or NH; Y 1>(CH 2) n; p, q : 0-2; and m, n : 1-3. [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Osteopathic; Cytostatic; Contraceptive; Antimicrobial; Virucide; Cardiovascular-Gen; Ophthalmological; Angiogenesis inhibitor; Antiinflammatory; Hepatotropic; Anti-HIV; Vasotropic; Antiarteriosclerotic; Dermatological; Neuroprotective; Nootropic; Nephrotropic; Antiallergic; Hypotensive; Immunomodulator. MECHANISM OF ACTION : Prostaglandin E2 receptor modulator. The ability of (I) to modulate prostaglandin E2 receptor was tested in mice using in-vitro method. The results showed that N-[2-(7-fluoro-2,4-dimethyl-1H-indole-3-yl)-ethyl]-2-(4-methoxy-phenoxy)-acetamide exhibited an IC 50value of 1.1 mu M.