CGRP antagonists

摘要

Nitrogen substituted six membered compounds (I), and their tautomers, diastereomers, enantiomers, hydrates, mixtures, salts, or hydrates of the salts, preferably salts with inorganic or organic acids or bases, are new. Nitrogen substituted six membered compounds of formula (I), and their tautomers, diastereomers, enantiomers, hydrates, mixtures, salts, or hydrates of the salts, preferably salts with inorganic or organic acids or bases, are new. Either R 1>spiro[indane-2,3'-pyrrolidine]-2'-one group; or R 2>H or 1-3C-alkyl; and R 1>R 2>N : 2,8-diazaspiro[4.5]decane group or piperidine group; R 3>a 6- or 10-membered aryl; ring A : six membered ring consisting of U 1>, V 1>, X and Y 1>; and U 1>, V 1>, X, Y 1>e.g. N,N-oxide. Where at most three residues of U 1>, V 1>, X or Y 1>are simultaneously N. With conditions. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. An independent claim is included for the preparation of a medicament comprising mixing (I) with one or more inert carrier and/or diluent, in a non-chemical manner. [Image] - ACTIVITY : Analgesic; Antimigraine; Antidiabetic; Cardiovascular-Gen.; Antidiarrheic; Dermatological; Vulnerary; Antiinflammatory; Respiratory Gen.; Gastrointestinal-Gen.; Antiarthritic; Antiallergic; Antiasthmatic; Vasotropic; Antibacterial; Immunosuppressive; Gynecological; Cytostatic; Endocrine-Gen.; Antilichen; Antipruritic; Osteopathic; Antirheumatic; Muscular-Gen.; Neuroprotective. - MECHANISM OF ACTION : Calcitonin gene-related peptide antagonist. The ability of (I) to antagonist calcitonin gene-related peptide was tested using SK-N-MC cell. The results showed that 4-methyl-6-(6-(2'-oxo-2',3'-dihydro-1'H -spiro[piperidin-4,4'-quinazolin]-1-yl)pyrimidin-4-carbonyl)benzo[d]o xazol-2(3H)-one exhibited an inhibitory constant value of 6 nM.