Patent EP-2003118-A1 (EP)
Inventor: BUCHMANN BERND
IPC: C07D209/14
Filed: 2007-06-13
Abstract: Cinnamic acid derivatives (I) and their isomers, diastereomers, enantiomers and salts and/or cyclodextrin clathrate, are new. Cinnamic acid derivatives of formula (I) and their isomers, diastereomers, enantiomers and salts and/or cyclodextrin clathrate, are new. A : 5-12C heteroaryl residue (optionally substituted with R4> and/or R3>), a phenyl residue (substituted with two residues in ortho-, meta or meta, para-position to each other), naphthyl residue (optionally substituted with OH, R4> or R1a), a phenyl residue (optionally substituted), where R4> is substituted with R1a; m : 1-3; R1a : -S(O)p-1-6C alkyl group or -S(O)p-3-6C cycloalkyl group, SO2NH2, SO2NH-CH3, CF3, COOH, 1-6C acyl- or NH-CO-1-6C alkyl residue, CN, -CONH2, 1-6C alkoxy group (substituted with CN, OH, 3-6C cycloalkyl, COOH, CONH2, CO2-(1-6C alkyl), CO-NH(1-6C alkyl), CO-N(1-6C alkyl)2, N-(1-6C alkyl)2 or NH-CO-1-6C alkyl), 1-6C alkyl (substituted with CN, OH, 3-6C cycloalkyl, COOH, CONH2, CO2-(1-6C alkyl), CO-NH(1-6C alkyl), CO-N(1-6C alkyl)2, N-(1-6C alkyl)2 or NH-CO-1-6C alkyl), O-6-12C aryl, O-5-16C heteroaryl, CO2-(1-6C alkyl), CO-NH(1-6C alkyl), CO-N(1-6C alkyl)2, 5-12C heteroaryl (substituted with halo, COOH, amino, CONH2, 1-6C alkyl, 1-6C acyl, 1-6C alkoxy, OH, CN, CO2-(1-6C alkyl), N-(1-6C alkyl)2, CO-NH(1-6C alkyl) or CO-N(1-6C alkyl)2), or 3-6C cycloalkyl (optionally substituted with halo, 1-6C alkyl, OH, CN, CO2-(1-6C alkyl), 1-6C alkyl, 1-6C acyl, N-(1-6C alkyl)2, CO-NH(1-6C alkyl), CO-N(1-6C alkyl)2 or 1-6C alkoxy); p : 0-2; R1>H or 1-6C alkyl (optionally substituted); R2>substituted 1-4C alkoxy or 1-6C alkyl, or H, halo, CN or -S(O)q-CH3; q : 0-2; either R3>, R4>H, halo, amino, -S(O)p-1-6C alkyl or -S(O)p-3-6C cycloalkyl, SO2NH2, SO2NH-CH3, COOH, CO-NH2, NH-CO-NH2, 1-6C acyl, NH-(1-6C alkyl), N-(1-6C alkyl)2 or NH-CO-1-6C alkyl residue, 1-6C alkyl (optionally substituted with 1-6C acyl, 1-6C alkoxy, OH, CN, CO2-(1-6C alkyl), N-(1-6C alkyl)2, COOH, CO-NH2, CO-NH(1-6C alkyl) or CON(1-6C alkyl)2), 1-6C alkoxy (optionally substituted with OH, CN, CO2-(1-6C alkyl), N-(1-6C alkyl)2, NH-3-6C cycloalkyl, COOH, CO-NH2, CO-NH(1-6C alkyl) or CON(1-6C alkyl)2), O-6-12C aryl, CH2-O-6-12C aryl, O-5-16C heteroaryl, OH, CN, CO2-(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 with T), 5-12C heteroaryl (optionally substituted with T), or 3-6C cycloalkyl (optionally substituted with halo, 1-6C alkyl, OH, CN, CO2-(1-6C alkyl), 1-6C alkyl, 1-6C acyl, N-(1-6C alkyl)2, COOH, CO-NH2, CO-NH(1-6C alkyl), CO-N(1-6C alkyl)2 or 1-6C alkoxy); or R3>R4> (in ortho, meta or meta, para-position) : -O-CO-S-, -S-CO-O-, CH2-CO-O-, O-CO-CH2-, -OCO- NH-, -NH-CO-O-, -CH2-CO-NH-, -NH-CO-CH2-, -CO-CH2-(CH2)m-, -CH2-(CH2)m-CO-, -O-(CH2)m-O- or -OC-(CH3)2-O-; T : halo, 1-6C alkyl, 3-6C cycloalkyl, 1-6C acyl, 1-6C alkoxy, OH, CN, CO2-(1-6C alkyl), N-(1-6C alkyl)2, COOH, CO-NH2, CO-NH(1-6C alkyl) or CO-N(1-6C alkyl)2; X : -C?=C- or -CH=CH-; Y1>-(CH2)n-; and n : 2-3. [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Osteopathic; Cytostatic; Contraceptive; Antimicrobial; Virucide; Cardiovascular-Gen; Ophthalmological; Angiogenesis inhibitor; Antiinflammatory; Hepatotropic; Anti-HIV; Vasotropic; Antiarteriosclerotic; Neuroprotective; Nootropic; Nephrotropic; Antiallergic; Hypotensive; Immunomodulator. MECHANISM OF ACTION : Prostaglandin E2 receptor modulator. The ability of (I) to modulate prostaglandin EP2 receptor was tested in mice using in-vitro method. The results showed that (E)-N-[2-(7-fluoro-2,4-dimethyl-1H-indol-3-yl)-ethyl]-3-(3-sulfamoyl-phenyl)-acrylamide exhibited an IC50 value of 1 mu M.