Inhibitors of the renal outer medullary potassium channel
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Abstract
Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.
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Citations
16 Claims
- 1. A compound of the formula I:
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12. A compound which is:
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5-{2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-2-benzofuran-1(3H)-one; 4-methyl-5-{2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-2-benzofuran-1(3H)-one; 3-methyl-4-(9-(2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)cyclobut-3-ene-1,2-dione; (R)-3-(9-(2-methoxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; 5-{(1S)-1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 4-(9-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 5-{(1R)-1-hydroxy-2-[9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 6-{(1S)-1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methoxypyridine-3-carbonitrile; (3R)-6-{1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-3-methyl-3,4-dihydro-1H-isochromen-1-one; (3S)-6-{(1R)-1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-3-methyl-3,4-dihydro-1H-isochromen-1-one; (3S)-6-{(1S)-1-hydroxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-3-methyl-3,4-dihydro-1H-isochromen-1-one; 4-(9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{2-hydroxy-2-[2-(1H-tetrazol-1-yl)pyrimidin-5-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridazin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridazin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[3-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[3-methyl-5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2R)-2-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-hydroxyethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-hydroxyethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undecan-2-one; 9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-3-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undecan-2-one; 9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-3-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undecan-2-one; 9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undecan-2-one; (R)-9-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-3-(5-oxo-2,5-dihydrofuran-3-yl)-1-oxa-3,9-diazaspiro[5.5]undecan-2-one; (R)-9-(2-hydroxy-2-(2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl)ethyl)-3-(5-oxo-2,5-dihydrofuran-3-yl)-1-oxa-3,9-diazaspiro[5.5]undecan-2-one; 5-{(1R)-1-hydroxy-2-[8-methyl-9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[8-methyl-9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-2-[(7R)-7-fluoro-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-2-[(7S)-7-fluoro-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 4-{9-[2-(4-bromophenyl)-2-hydroxyethyl]-3,9-diazaspiro[5.5]undec-3-yl}-3-methylfuran-2(5H)-one; 5-{(1R)-1-hydroxy-2-[9-(2-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-2-[9-(4-fluoro-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 3-fluoro-4-(9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 5-{(1R)-2-[9-(4-chloro-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[9-(5-oxo-4-phenyl-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[9-(5-oxo-4-pyridin-4-yl-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 3-cyclopropyl-4-(9-{2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 5-{(1R)-2-[9-(4-cyclopropyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 4-(9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[5-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-hydroxyethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-hydroxyethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-hydroxy-1-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{2-hydroxy-1-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[3-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[3-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[2-(1H-tetrazol-1-yl)pyridin-4-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[2-(1H-tetrazol-1-yl)pyridin-4-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[5-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[5-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyrazin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[6-(1H-tetrazol-1-yl)pyrazin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[4-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2R)-2-hydroxy-2-[4-(1H-tetrazol-1-yl)pyridin-2-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 4-(9-{(2S)-2-hydroxy-2-[2-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-3-methylfuran-2(5H)-one; 3-(9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)cyclopent-2-en-1-one; 3-(9-{(2S)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)cyclopent-2-en-1-one; 5-{(1R)-1-hydroxy-2-[9-(3-oxocyclopent-1-en-1-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 3-(9-{2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)cyclopent-2-en-1-one; 3-(9-{(2R)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-2-methylcyclopent-2-en-1-one; 3-(9-{(2S)-2-hydroxy-2-[2-methyl-6-(1H-tetrazol-1-yl)pyridin-3-yl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-2-methylcyclopent-2-en-1-one; 5-{(1R)-1-hydroxy-2-[9-(2-methyl-3-oxocyclopent-1-en-1-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 3-(9-{(2R)-2-hydroxy-2-[2-methyl-4-(1H-tetrazol-1-yl)phenyl]ethyl}-3,9-diazaspiro[5.5]undec-3-yl)-2-methylcyclopent-2-en-1-one; 3-{9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl}-3,9-diazaspiro[5.5]undec-3-yl]-4-methylcyclobut-3-ene-1,2-dione; (R)-3-ethyl-4-(9-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)cyclobut-3-ene-1,2-dione; (R)-3-cyclopropyl-4-(9-(2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)cyclobut-3-ene-1,2-dione; (R)-3-(9-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (S)-3-(9-(2-(6-(1H-tetrazol-1-yl)pyridin-3-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (S)-3-(9-(2-(6-(1H-tetrazol-1-yl)pyridazin-3-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (R)-3-(9-(2-(6-(1H-tetrazol-1-yl)pyridazin-3-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (S)-3-(9-(2-(5-(1H-tetrazol-1-yl)pyrazin-2-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (R)-3-(9-(2-(5-(1H-tetrazol-1-yl)pyrazin-2-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (S)-3-(9-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)-2-hydroxyethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (R)-3-(9-(2-hydroxy-2-(tetrazolo[1,5-a]quinolin-7-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; (S)-3-(9-(2-hydroxy-2-(tetrazolo[1,5-a]quinolin-7-yl)ethyl)-3,9-diazaspiro[5.5]undecan-3-yl)-4-methylcyclobut-3-ene-1,2-dione; 5-{(1S)-1-methoxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-methoxy-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-2-[9-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[9-(6-oxo-3,6-dihydro-2H-pyran-4-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[(7R)-7-hydroxy-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[(7R)-7-(methoxymethoxy)-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[(7S)-7-(methoxymethoxy)-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[(7R)-7-methoxy-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 5-{(1R)-1-hydroxy-2-[(7S)-7-methoxy-9-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one; 4-(9-{[6-(1H-tetrazol-1-yl)pyridin-3-yl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{[2,6-difluoro-4-(1H-tetrazol-1-yl)phenyl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{[5-fluoro-6-(1H-tetrazol-1-yl)pyridin-3-yl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{[3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl]carbonyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-(9-{[2,5-difluoro-4-(1H-tetrazol-1-yl)phenyl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one; 4-methyl-5-{2-oxo-2-[9-(5-oxo-2,5-dihydrofuran-3-yl)-3,9-diazaspiro[5.5]undec-3-yl]ethyl}-2-benzofuran-1(3H)-one; 4-(9-{[5-(1H-tetrazol-1-yl)pyrazin-2-yl]acetyl}-3,9-diazaspiro[5.5]undec-3-yl)furan-2(5H)-one;
ora pharmaceutically acceptable salt thereof.
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Specification