Inhibitors of the renal outer medullary potassium channel

摘要

This invention relates to compounds having structural Formula (I); and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir 1.1). The compounds of Formula I are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure.;

主权项

1. A compound 1 selected from the group consisting of:
5-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 1-{4-[2-(2,1,3-benzoxadiazol-5-yl)ethyl]piperazin-1-yl}-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone, 6-methyl-5-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 4-methyl-5-[2-(4-{[(7R)-3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl]carbonyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 4-methyl-5-[2-(4-{[(75)-3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl]carbonyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 4-[(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)methyl]-3,4-dihydro-2H-chromene-8-carbonitrile, 4-({4-[(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetyl]piperazin-1-yl}methyl)-3,4-dihydro-2H-chromene-8-carbonitrile, 5-[2-(4-{[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 4-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile, 5-[2-(4-{[5-(1H-tetrazol-1-yl)biphenyl-2-yl]acetyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 5-[2-(4-{[2-cyclopropyl-4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-2-benzofuran-1(3H)-one, 2-methoxy-4-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile, 1-{4-[2-(3-nitrophenyl)ethyl]piperazin-1-yl}-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone, 5-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)propyl]-2-benzofuran-1(3H)-one, 5-[1-4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)propan-2-yl]-2-benzofuran-1(3H)-one, 6-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile, 1-{4-[1-(2,1,3-benzoxadiazol-5-yl)propan-2-yl]piperazin-1-yl}-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone, 6-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)-5,6,7,8-tetrahydronaphtho[2,3-c]furan-1(3H)-one, 1-{4-[2-(2,1,3-benzoxadiazol-5-yl)-2-fluoro ethyl]piperazin-1-yl}-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone, 6-fluoro-2-methyl-3-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile, 6-[1-hydroxy-2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one, 6-[1-hydroxy-2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-3-methyl-3,4-dihydro-1H-isochromen-1-one, 6-[(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)methyl]-8,9-dihydro-1H-furo[3,4-j]isochromen-3(614)-one, 5-fluoro-2-methoxy-4-(2-oxo-2-{4-[(3-oxo-3,6,8,9-tetrahydro-1H-furo[3,4-j]isochromen-6-yl)methyl]piperazin-1-yl}ethyl)benzonitrile, 3-methyl-6-[2-(3-methyl-4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one, (3R)-3-methyl-6-[2-(4-{[6-(1H-tetrazol-1-yl)pyridin-3-yl]acetyl}piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one, (3S)-3-methyl-6-[2-(4-{[6-(1H-tetrazol-1-yl)pyridin-3-yl]acetyl}piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one, or 5-(2-oxo-2-{4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-2-(1H-tetrazol-1-yl)benzonitrile, or a pharmaceutically acceptable salt thereof.