N-(1-Phthalazin-1-yl-piperidin-4-yl)-amides as EP2-receptor modulators

摘要

N-(1-Phthalazin-1-ylpiperidin-4-yl)amides, and its isomers, salts, and cyclodextrin clathrates are new. N-(1-Phthalazin-1-ylpiperidin-4-yl)amides of formula (I), and its isomers, salts, and cyclodextrin clathrates are new. W 1H, or 1-4C alkyl; X 1(CH 2) n, 2-4C alkenyl, or 2-4C alkynyl; n : 0-4; R 15-12-membered mono- or bicyclic aryl or heteroaryl ring, 5-12-membered mono- or bicyclic O-aryl or O-heteroaryl ring, S-aryl or S-heteroaryl ring, N-aryl or N-heteroaryl ring (all optionally mono- to trisubstituted), 1-6C alkyl, 3-10C cycloalkyl or 8-12-membered fused (hetero)arylcycloalkyl radical (all optionally substituted); R 2-R 51-6C alkyl, 3-10C cycloalkyl ring, 2-6C alkenyl, or 5-12-membered mono- or bicyclic aryl, heteroaryl ring (all optionally substituted), H, halogen, cyano, or OR 6, OC(O)R 6, S(O) n1R 6, SO 2NHR 6, SO 2NHC(O)R 6, NR 6R 7, NHC(O)R 6, CH 2NR 6R 7, CH 2NHC(O)R 6, C(OH)R 6R 7, C(O)R 6, CO 2R 6, or C(O)NR 6R 7; n 10-2; R 6and R 71-6C alkyl, 3-10C cycloalkyl ring, 5-12-membered mono- or bicyclic heteroaryl ring (all optionally substituted), H or 5-12-membered mono- or bicyclic aryl or heteroaryl ring; and R 6+R 73-8-membered ring. [Image] ACTIVITY : Antiinfertility; Gynecological; Cytostatic; Analgesic; Antimicrobial; Virucide; Antiinflammatory; Hepatotropic; Anti-HIV; Cardiovascular-Gen.; Vasotropic; Ophthalmological; CNS-Gen.; Respiratory-Gen.; Antiangiogenic; Neuroprotective; Nootropic; Immunomodulator; Nephrotropic. MECHANISM OF ACTION : Prostaglandin (EP 2) receptor modulator; EP 2receptor agonist; EP 2receptor antagonist. Compound -N-[1-(6-bromo-phthalazin-1-yl)-piperidin-4-yl]-2,3-dichloro-benzamide (Ia) was tested for EP 2receptor antagonist activity using cAMP antagonism assay. The compound (Ia) showed IC 50of 0.2 mu m.