New 8-dihydropyridyl-chromene derivatives, are antagonists of the mineralcorticoid receptor, useful for treatment and prevention of e.g. aldosteronism, hypertension and cardiac insufficiency

摘要

8-Dihydropyridyl-4-oxo-4H-chromene derivatives (I), their salts, solvates and solvated salts are new. 8-Dihydropyridyl-4-oxo-4H-chromene derivatives of formula (I), their salts, solvates and solvated salts are new. R1 and R21-4C alkyl, trifluoromethyl, cyclopropyl or cyclobutyl; R31-4C alkyl (optionally substituted by 1-3 fluoro), phenyl (optionally substituted by halo, cyano, 1-4C alkyl, trifluoromethyl, 1-4C alkoxy or trifluoromethoxy) or 3-7C cycloalkyl; R41-6C alkyl, optionally substituted by 3-7C cycloalkyl or by 1-3 fluoro, phenyl, 5- or 6-membered heteroaryl, where phenyl and heteroaryl may be substituted by halo, cyano, 1-4C alkyl or alkoxy, trifluoromethyl or trifluoromethoxy; R5hydrogen, halo, cyano, nitro, trifluoromethyl, 1-4C alkyl or 1-4C alkoxy; and R6hydrogen or fluoro. An independent claim is included for four preparations of (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Cerebroprotective; Antidiabetic; Neuroprotective; Antiinflammatory; Vasotropic. MECHANISM OF ACTION : (I) Are selective antagonists of the mineralcorticoid receptor. 8-[3-Acetyl-2,6-dimethyl-5-(4-methylpentanoyl)-1,4-dihydropyridin-4-yl]-2-methyl-4H-chromen-4-one (Ia) has IC50 of 111 nM at the human mineralcorticoid receptor, expressed recombinantly in Chinese hamster ovary cells.