CGRP antagonists, their preparation and use as a medicament

摘要

Calcitonin gene related peptide antagonists, comprising 2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl-piperidine compounds (I) and their tautomers, diastereomers, enantiomers, hydrates or salts, preferably salts with inorganic or organic acids or bases, are new. Calcitonin gene related peptide antagonists, comprising 2-oxo-1,2,4,5-tetrahydro-1,3-benzdiazepin-3-yl-piperidine compounds of formula (I) and their tautomers, diastereomers, enantiomers, hydrates or salts, preferably salts with inorganic or organic acids or bases, are new. B 1> = 3,5-dichloro-4-hydroxyphenyl, 3,5-dibromo-4-hydroxyphenyl, 3-chloro-4-hydroxyphenyl, 3-bromo-4-hydroxyphenyl, 3,5-dimethyl-4-hydroxyphenyl, 4-amino-3,5-dimethylphenyl, 3,5-di(trifluoromethyl)-phenyl, 3-trifluoromethylphenyl and m-tolyl; NR 1>+R 2> = cyclic group of formula (A); Y 1> = C; or N when R 4> is a free electron pair; R 3> = cyclopentyl-, cyclohexyl-, or cycloheptyl group, or a heterocycle selected from a morpholin-4-yl-, 1,1-dioxothiomorpholin-4-yl-, piperidin-1-yl-, piperidin-4-yl-, piperazin-1-yl- or pyrrolidin-1-yl group, (where the monocyclic heterocycle is optionally substituted with 1-2 of OH, CH 3, ethyl, trifluoromethyl, hydroxymethyl, or hydroxyethyl; and/or is optionally mono-substituted with hydroxycyclopropyl, trifluormethylcarbonylmethyl, amino, carboxy-carbonyl, methoxycarbonyl, ethoxycarbonyl-carbonyl, carboxymethyl, carboxyethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, carboxy-ethylcarbonyl, ethoxycarbonyl-ethylcarbonyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, (hydroxyamino)-carbonylmethyl, hydroxy-(methyl)-aminocarbonyl-methyl or methoxyaminocarbonyl-methyl, where the substituents may be at a carbon or a nitrogen atom; and/or is optionally mono-substituted by a carboxy group, which may not be at a nitrogen atom); and R 4> = H (if Y 1> represents C) or free electron pair (if Y 1> represents N). Independent claims are included for: (1) preparations of (I); and (2) physiologically compatible salts of (I) with inorganic or organic acids or bases. [Image] [Image] - ACTIVITY : Analgesic; Antimigraine; Antidiabetic; Cardiovascular-Gen.; Antidiarrheic; Dermatological; Antiinflammatory; Antiarthritic; Antiallergic; Antiasthmatic; Respiratory-Gen.; Vasotropic; Antibacterial; Immunosuppressive; Gastrointestinal-Gen.; Cytostatic. - MECHANISM OF ACTION : Calcitonin gene related peptide antagonist.