3, 4 - SUBSTITUTED PIPERIDINE DERIVATIVES AS RENIN INHIBITORS

摘要

Disclosed are trans-4-(2-oxo-1,2-dihydro-pyridin-4-yl)-3-piperidinecarboxamide derivatives as represented by the general formula (I), wherein the substituents are as defined in the specification. Representative compounds include trans-N-[2-chloro-3,5-bis(3-methoxypropyl)benzyl]-N-cyclopropyl-4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl)-3-piperidinecarboxamide, trans-N-{ 3-bromo-5-[3-(difluoromethoxy)propyl]-4-methylbenzyl} -N-cyclopropyl-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-3-piperidinecarboxamide, trans-N-({ 3-bromo-4-methyl-5-[3-(methyloxy)propyl]phenyl} methyl)-N-cyclopropyl-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-3-piperidinecarboxamide, trans-N-Cyclopropyl-N-( { 2,3-dimethyl-5-[3-(methyloxy)propyl]phenyl} methyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-3-piperidinecarboxamide, trans-N-Cyclopropyl-N-({ 4-fluoro-1-[(3-fluorophenyl)methyl]-1H-indol-3 -yl]methyl} -4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-3-piperidinecarboxamide and trans-N-cyclopropyl-N-({ 2,3-dichloro-5-[3-(methyloxy)propyl] phenyl} methyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-3-piperidinecarboxamide. Further disclosed is a pharmaceutical composition which comprises an effective amount of a compound as defined above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the treatment or prophylaxis of diseases which are related to hypertension, congestive heart failure, pulmonary hypertension, renal insufficiency, renal ischemia, renal failure, renal fibrosis, cardiac insufficiency, cardiac hypertrophy, cardiac fibrosis, myocardial ischemia, cardiomyopathy, glomerulonephritis, renal colic, complications resulting from diabetes, glaucoma, elevated intra-ocular pressure, atherosclerosis, restenosis post angioplasty, complications following vascular or cardiac surgery, erectile dysfunction, hyperaldosteronism, lung fibrosis, scleroderma, anxiety, cognitive disorders, complications of treatments with immunosuppressive agents, and other diseases known to be related to the renin-angiotensin system.