New 4-heterocyclyl-1-acyl-piperidine derivatives, useful e.g. for treating headache, diabetes and cardiovascular disease, are antagonists of calcitonin-gene related peptide

摘要

4-heterocyclyl-1-acyl-piperidine derivatives (I), their tautomers, diastereomers, enantiomers, hydrates and/or (hydrated) salts are new. 4-heterocyclyl-1-acyl-piperidine derivatives of formula (I), their tautomers, diastereomers, enantiomers, hydrates and/or (hydrated) salts are new A and B each : N or CH; D : hydrogen or Me; E : hydrogen, fluoro, chloro, bromo, Me, Et or trifluoromethyl; X : CH2 or NH; R12-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl or 5-oxo-3-phenyl-4,5-dihydro-1,2,4-triazol-1-yl; R24-Ra-piperidin-1-yl, 4-Rb-piperazin-1-yl or 4-Rc-perhydro-1,4-diazepin-1-yl; Ra : piperidin-1-yl, piperidin-4-yl (optionally N-substituted by Me, methoxycarbonylmethyl or methylsulfonyl), dimethylamino, piperazin-1-yl (optionally 4-methyl substituted), pyrrolidin-1-yl, perhydro-1,4-diazepin-1-yl (optionally 4-methyl substituted) or 4-fluorophenyl; Rb : piperidin-4-yl (optionally 4-methyl substituted), pyridin-4-yl or 4-fluorophenyl; Rc : piperidin-4-yl, optionally N-methyl substituted) . An independent claim is also included for 5 methods of preparing (I). [Image] ACTIVITY : Antimigraine; Analgesic; Antidiabetic; Cardiant; Antidiarrhea; Dermatological; Antiinflammatory; Antiarthritic; Antiallergic; Antiasthmatic; Antibacterial; Immunosuppressive; Gynecological; Cytostatic. No details of tests for these activities are given. MECHANISM OF ACTION : (I) are selective antagonists of calcitonin-gene related peptide, with IC50 below 104 nM.