New 4-pyrroloisoindolyl-substituted dihydropyridine derivatives, useful as antagonists of the mineralcorticoid receptor for treating e.g. aldosteronism, hypertension and stroke

摘要

4-Pyrroloisoindolyl-substituted dihydropyridine derivatives (I) and their salts, solvates and solvated salts are new. 4-Pyrroloisoindolyl-substituted dihydropyridine derivatives of formula (I) and their salts, solvates and solvated salts are new . R1 and R21-4C alkyl, trifluoromethyl, cyclopropyl or cyclobutyl; R3cyano, nitro or R7CO; R71-6C alkyl (optionally substituted by 3-7C cycloalkyl or by 1-3 fluoro), phenyl (optionally substituted by halo, cyano, 1-4C alkyl, trifluoromethyl, 1-4C alkoxy or trifluoromethoxy) or 3-7C cycloalkyl; R43-7C cycloalkyl or 1-6C alkyl, optionally substituted by 3-7C cycloalkyl or by 1-3 fluoro; R5hydrogen, halo, cyano, nitro, trifluoromethyl or 1-4C alkyl or alkoxy; and R6hydrogen or fluoro. An independent claim is included for two preparations of (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Vasotropic; Neuroprotective; Antidiabetic. MECHANISM OF ACTION : Selective antagonism of the mineralcorticoid receptor. Isopropyl 5-cyano-2,6-dimethyl-4-(5-oxo-5H-pyrrolo[2,1-a]isoindol-9-yl)-1,4-dihydropyridine-3-carboxylate has IC50 of 148 nM at the human mineralcorticoid receptor, expressed recombinantly in Chinese hamster ovary cells.