NOVEL DERIVATIVES OF PYRAZOLE, METHOD OF OBTAINING THEM, PHARMACEUTIC AGENT, APPLICATION OF SUCH DERIVATIVES IN PRODUCTION OF A PHARMACEUTIC AGENT AND METHOD OF OBTAINING SUCH PHARMACEUTIC AGENT

摘要

New 3-(2-furyl)indazole derivatives useful as soluble guanylate cyclase activators, e.g. for treating cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension 3-(2-Furyl)indazole derivatives of formula (I) and their stereoisomers and salts are new. X = O; R1 = 1-10C alkyl or hydroxyalkyl; R1a = H; R2, R3 = groups forming a benzene ring (optionally substituted with R5); R4 = 6-14C aryl or 5- or 6-membered heteroaryl (optionally substituted with R5); n = 0-2; R5 = halo, 1-5C alkyl, OR6, NR7R8, COOR9, COR10, CONR11R12, CON(R12)OR11, SOmR13, SO2NR14R15, NO2, CN or CF3; R6, R7, R8, R11, R14 = H, R, COR16 or SO2R17; R9, R10, R12, R13, R15 = H or R; R = 1-10C alkyl, 6-14C aryl, (6-14C)aryl(1-4C)alkyl, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-4C)alkyl, Het or Het(1-4C)alkyl, all optionally substituted with halo, 1-5C alkyl, OR18, NR19R20, COOR21, COR22, CONR23R24, CON(R24)OR23, SOmR25, SO2NR26R27, NO2, CN or CF3; Het = 5- to 7-membered heterocyclyl; R16 = H, 1-6C alkyl or R'; R17 = 1-6C alkyl or R'; R18, R19, R20, R23, R26 = H, 1-10C alkyl, R', COR16 or SO2R17; R21, R22, R24, R25, R27 = H, 1-10C alkyl or R'; R' = 6-14C aryl, (6-14C)aryl(1-4C)alkyl, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-4C)alkyl, Het or Het(1-4C)alkyl; NR7R8, NR11R12, NR14R15, NR19R20, NR23R24, NR26R27 = 5- to 7-membered heterocyclyl optionally containing another heteroatom (N, O or S) and optionally substituted with 1-4C alkyl or halo; and m = 0-2. Provided that R1 is not CH2OH in the 5 position when R2+R3 forms a benzene ring optionally monosubstituted with 1-3C alkyl, halo, OH or 1-3C alkoxy, n = 1 and R4 = phenyl optionally monosubstituted with 1-3C alkyl, halo, OH or 1-3C alkoxy. An Independent claim is also included for preparation of (I).