Patent EP-2149552-A1 (EP)
Inventor: BUCHMANN DR BERND
IPC: A61K31/404
Filed: 2008-07-30
Abstract: 5,6-Substituted benzamide derivatives of formula (I) and their isomers, diasteromers, enantiomers, salts and/or cyclodextrin clathrates, are new, where (I) excludes compound (in which R 1>and R 5>are methyl, and R 3>is chlorine), e.g. N-[2-(2-methyl-1H-indol-3-yl)ethyl]-2-(2-methylpropoxy)-benzamide, N-[2-[2-methyl-5-(trifluoromethyl)-1H-indol-3-yl]ethyl]-2-thiophenecarboxylic acid amide, 4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]-benzamide, and N-[2-[5-(chlorodifluoromethoxy)-2-methyl-1H-indol-3-yl]ethyl]-3,4-dimethoxy-benzamide. 5,6-Substituted benzamide derivatives of formula (I) and their isomers, diasteromers, enantiomers, salts and/or cyclodextrin clathrates, are new, where (I) excludes compound (in which R 1>and R 5>are methyl, and R 3>is chlorine), preferably 43 amide compounds e.g. N-[2-(2-methyl-1H-indol-3-yl)ethyl]-2-(2-methylpropoxy)-benzamide, N-[2-[2-methyl-5-(trifluoromethyl)-1H-indol-3-yl]ethyl]-2-thiophenecarboxylic acid amide, 4-chloro-N-[2-(5-methoxy-2-methyl-1H-indol-3-yl)ethyl]-benzamide, N-[2-[5-(chlorodifluoromethoxy)-2-methyl-1H-indol-3-yl]ethyl]-3,4-dimethoxy-benzamide, 2,4-dichloro-N-[2-(5-fluoro-2-methyl-1H-indol-3-yl)ethyl]-benzamide, N-[2-(2,5-dimethyl-1H-indol-3-yl)ethyl]-2-methyl-7-benzoxazole carboxylic acid amide, N-[2-(2,5-dimethyl-1H-indol-3-yl)ethyl]-2,3-dihydro-thieno[3,4-b]-1,4-dioxin-5-carboxylic acid amide, N-[2-(2,5-dimethyl-1H-indol-3-yl)ethyl]-5-ethyl-thieno[2, 3-b]thiophen-2-carboxylic acid amide, 2-methyl-N-[2-[2-methyl-5-(trifluoromethoxy)-1H-indol-3-yl]ethyl]-7-benzoxazole carboxylic acid amide, and N-[2-(5-fluoro-2-methyl-1H-indol-3-yl)ethyl]-2-methyl-7-benzoxazole carboxylic acid amide. A : 6-12C-aryl or 5-12C-heteroaryl (optionally substituted); R 1>optionally substituted 1-6C-alkyl; R 2>1-4C-alkoxy or 1-6C-alkyl (optionally substituted), H, halo, CN or -S(O) q-CH 3; R 3>H, halo, 1-6C-alkyl, CN, 1-6C-alkoxy, or 6-12C-aryl; R 4>H, halo, CN, 1-6C-alkyl, 1-6C-alkoxy, or 6-12C-aryl; R 5>H, halo, CN or 1-6C-alkyl; q : 0-2; Y 1>-(CH 2) n; and n : 1-3. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. Independent claims are included for: (1) a medicament comprising (I) in combination with a cyclooxygenase inhibitor, preferably aspirin, naproxen, indomethacin, meloxicam, celecoxib, ibuprofen, parecoxib, rofecoxib, valdecoxib, NS-398, lumiracoxib, ceracoxib or etoricoxib; and (2) the preparation of (I). [Image] ACTIVITY : Antiinfertility; Gynecological; Analgesic; Osteopathic; Cytostatic; Neuroprotective; Nootropic; Antiparkinsonian; Antiinflammatory; Gastrointestinal-Gen.; Antiulcer; Nephrotropic; Antiarteriosclerotic; Respiratory-Gen.; Antimicrobial; Contraceptive; Antiparasitic; Virucide; Hepatotropic; Anti-HIV; Immunomodulator; Cardiovascular-Gen.; Vasotropic; Ophthalmological; Angiogenesis Modulator. MECHANISM OF ACTION : Prostaglandin E2 receptor modulator. The prostaglandin E2 receptor antagonistic activity of (I) was tested in human prostaglandin E2 receptor signals. The results showed that 5-chloro-1H-indol-2-carboxylic acid-[2-(6,7-difluoro-2-methyl-1H-indol-3-yl)-ethyl]-amide exhibited an IC 50value of 0.071 mu M.