New N-acylalkoxycarbonyl-piperidine derivatives, useful as CGRP antagonists, for treating e.g. headaches, cardiovascular disease, skin disorders, morphine tolerance, and inflammatory diseases such as osteoarthritis and allergic rhinitis

摘要

4-Substituted-N-alkoxycarbonyl-piperidine derivatives (I), and their tautomers, diastereomers, enantiomers, hydrates, mixtures, acid and base salts and hydrated salts, are new. 4-Substituted-N-alkoxycarbonyl-piperidine derivatives of formula (I), and their tautomers, diastereomers, enantiomers, hydrates, mixtures, acid and base salts and hydrated salts, are new. R 12-oxo-1,2,3,4-tetrahydroquinazolin-3-yl, 2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl (optionally substituted by R 1.1 on phenyl) or 3-oxo-5-phenyl-2,3-dihydro-1,2,4-triazol-2-yl; R 23-chloro-4-(amino or hydroxy)-5-(methyl or trifluoromethyl)-phenyl; R 1.1H or methoxy; R 3group of formula (a); X, Y' : N or C; R 3.1H, 1-3C alkyl or R 3.1.1CO; R 4group of formula (b)-(e); R 3.2, R 4.1electron pair, H or 1-3C alkyl; R 4.2H, 1-3C alkyl or R 4.2.1; R 3.1.1, R 4.2.1hydroxy or 1-6C alkoxy; R 4.3hydroxy, 1-6C alkyl, amino(2-4C) alkylenyl, aminocarbonyl(1-3C)alkylenyl (both optionally (di)1-3C alkylamino) or R 4.3.1-(2-4C)alkylenyl; R 4.3.1pyrrolidinyl, piperidinyl, morpholino, 2-oxo-pyrrolidinyl or 2-oxopiperidinyl (all bonded through N); R 5.1R 5.1.1-OCO, R 5.1.1-OCO-(1-3C)alkylenyl-NH, R 5.1.1-OCO-(1-3C)alkylenyl-O, R 5.1.1-OCO-(1-3C)alkylenyl-, R 5.1.1-OCO-CO- or R 5.1.1-OCO-(1-3C)alkylenyl-CO-; R 5.1.1H, 1-8C alkyl, phenyl, indanyl, Q1-(1-3C)alkylenyl Q2-(2-4C)alkylenyl ; Q1 : pyridyl, aminocarbonyl (optionally substituted by 1 or 2 1-6C alkyl), 1-6C alkylcarbonyloxy, 1-6C alkoxycarbonyloxy or R 5.1.1.1-carbonyl; Q2 : hydroxy, 1-6C alkoxy, amino (optionally substituted by 1 or 2 1-6C alkyl) or R 5.1.1.2; R 5.1.1.1pyrrolidino or piperidino; R 5.1.1.2R 4.3.1; R 5.2R 5.1; and provided that: (i) when X is N, then R 3.2 is an electron pair; (ii) when X is C, then R 3.2 is H or 1-3C alkyl; (iii) when Y is N, then R 4.1 is a free electron pair; (iv) when Y is C, then R 4.1 is H or 1-3C alkyl; and (v) X and Y are not both N. [Image] [Image] ACTIVITY : Analgesic; Antidiabetic; Cardiant; Antidiarrhea; Dermatological; Antiinflammatory; Osteopathic; Antirheumatic; Antiarthritic; Antiasthmatic; Antibacterial; Immunosuppressive; Neuroprotective; Gynecological. Test methods are described but no results for specific compounds is given. MECHANISM OF ACTION : CGRP (calcitonin gene-related peptide) antagonist. Test methods are described but no results for specific compounds is given.