Indolyl alkyl thieno-pyrimidyl amines as modulators of EP2 receptors

摘要

Indolylalkylthienopyrimidylamine derivatives are new. Indolylalkylthienopyrimidylamine derivatives of formula (I), their stereoisomers, diastereomers, enantiomers, salts and their cyclodextrin clathrates, are new. R 1CH=CH-aryl having 6-10-membered mono- or bicyclic aryl ring, CH=CH-heteroaryl having 5-10-membered mono- or bicyclic heteroaryl ring, 6-10-membered mono- or bicyclic aryl ring, or 5-10-membered mono- or bicyclic heteroaryl ring, (all optionally mono- to tri-substituted by G 1), H, halo or 1-4C alkyl; G 1halo, cyano, CH 2CN, R 6, OR 6, CH 2OR 6, OC(O)R 6, S(O) nR 6, SO 2NHR 6, SO 2NHC(O)R 6, NR 6R 7, NHC(O)R 6, NHSO 2R 6, CH 2NR 6R 7, CH 2NHC(O)R 6, C(OH)R 6R 7, C(O)R 6, CO 2R 6or C(O)NR 6R 7; n : 0-2; R 2, R 3and R 7H or 1-4C alkyl; R 4and R 5H, halo, cyano, 1-4C alkyl; R 6H, 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl, 3-6C cycloalkyl, CH 2-3-6C cycloalkyl, 6-membered aryl ring, 5-6-membered heteroaryl ring, or CH 2-(hetero)aryl (where the aryl radical is 6-membered and the heteroaryl radical is 5- or 6-membered);or NR 6R 73-6-membered ring. Independent claims are included for the following: (1) medicaments comprise at least one of the compound (I); and (2) preparation of the compound (I). [Image] ACTIVITY : Antiinfertility; Gynecological; Cytostatic; Analgesic; Osteopathic; Antiinflammatory; Contraceptive; Antimicrobial; Virucide; Cardiovascular-Gen.; Ophthalmological; Antiangiogenic; Neuroprotective; Immunomodulator; Nephrotropic; Antiparasitic; Hepatotropic; Anti-HIV; Vasotropic; Antiarteriosclerotic; Nootropic. MECHANISM OF ACTION : Prostaglandin E2 (EP2) receptor modulator; EP2 receptor antagonist; EP2 receptor agonist. The efficacy of [6-(2,5-difluorophenyl)thieno[3,2-d]pyrimidin-4-yl]-[2-(7-fluoro-2,4-dimethyl-1H-indol-3-yl)ethyl]amine (I') was evaluated for EP2 receptor antagonistic activity using antagonism assay on human. The compound (I') showed IC 50of 0.097 mu M.