CPC C07D 498/08 (2013.01) [A61K 31/42 (2013.01); A61K 31/422 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); C07D 207/34 (2013.01); C07D 213/79 (2013.01); C07D 213/80 (2013.01); C07D 213/81 (2013.01); C07D 231/14 (2013.01); C07D 233/26 (2013.01); C07D 233/90 (2013.01); C07D 237/04 (2013.01); C07D 237/24 (2013.01); C07D 239/34 (2013.01); C07D 239/36 (2013.01); C07D 241/24 (2013.01); C07D 249/04 (2013.01); C07D 249/08 (2013.01); C07D 249/10 (2013.01); C07D 249/12 (2013.01); C07D 249/18 (2013.01); C07D 257/04 (2013.01); C07D 261/12 (2013.01); C07D 261/18 (2013.01); C07D 261/20 (2013.01); C07D 263/34 (2013.01); C07D 263/56 (2013.01); C07D 271/06 (2013.01); C07D 277/46 (2013.01); C07D 277/56 (2013.01); C07D 307/68 (2013.01); C07D 333/40 (2013.01); C07D 333/70 (2013.01); C07D 401/04 (2013.01); C07D 401/06 (2013.01); C07D 403/04 (2013.01); C07D 403/06 (2013.01); C07D 405/12 (2013.01); C07D 409/06 (2013.01); C07D 413/04 (2013.01); C07D 413/06 (2013.01); C07D 413/12 (2013.01); C07D 471/04 (2013.01); C07D 498/04 (2013.01)] | 19 Claims |
1. A method of treating a disease mediated, at least in part by, neprilysin in a subject in need thereof, comprising administering to the subject an effective amount of a compound selected from:
(a) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-hydroxyisoxazole-5-carbonyl)amino]pentanoic acid ethyl ester;
(b) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-hydroxyisoxazole-5-carbonyl)amino]pentanoic acid;
(c) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-hydroxyisoxazole-5-carbonyl)amino]pentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester;
(d) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(3-methoxyisoxazole-5-carbonyl)amino]-pentanoic acid;
(e) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(4-chlorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(f) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[3-(2-methoxy-benzoylamino)-isoxazole-5-carbonyl]-amino}-pentanoic acid;
(g) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(2-chlorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(h) (2R,4R)-5-Biphenyl-4-yl-4-[(3-cyclohexyl-isoxazole-5-carbonyl)-amino]-2-hydroxy-pentanoic acid;
(i) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(3-fluorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(j) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(2-fluorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(k) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[3-(1-methyl-1H-pyrazol-4-yl)-isoxazole-5-carbonyl]-amino}-pentanoic acid;
(l) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(2,5-dichlorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(m) (2R,4R)-5-Biphenyl-4-yl-4-{[3-(3,4-dichlorophenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(n) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[3-(2-methoxy-phenyl)-isoxazole-5-carbonyl]-amino}-pentanoic acid;
(o) 5-((1R,3R)-1-Biphenyl-4-ylmethyl-3-carboxy-3-hydroxy-propylcarbamoyl)-isoxazole-3-carboxylic acid;
(p) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(2-methoxy-phenyl)-isoxazole-3-carbonyl]-amino}-pentanoic acid;
(q) (2R,4R)-5-Biphenyl-4-yl-4-{[5-(2-chlorophenyl)-isoxazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(r) (2R,4R)-5-Biphenyl-4-yl-4-{[5-(4-chlorophenyl)-isoxazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(s) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(3-methoxy-phenyl)-isoxazole-3-carbonyl]-amino}-pentanoic acid;
(t) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(5-morpholin-4-ylmethyl-isoxazole-3-carbonyl)-amino]-pentanoic acid;
(u) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(4-methoxy-phenyl)-isoxazole-3-carbonyl]-amino}-pentanoic acid;
(v) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(2-hydroxy-phenyl)-isoxazole-3-carbonyl]-amino}-pentanoic acid;
(w) (2R,4R)-5-Biphenyl-4-yl-4-{[5-(2-chlorobenzoylamino)-isoxazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid;
(x) (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-[(2-phenyl-oxazole-5-carbonyl)-amino]-pentanoic acid;
(y) (2R,4R)-4-[(3-Acetyl-isoxazole-5-carbonyl)-amino]-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-pentanoic acid;
(z) (2R,4R)-5-(3′-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-methoxy-isoxazole-5-carbonyl)-amino]-pentanoic acid;
(aa) (2R,4R)-5-(3′-Chloro-biphenyl-4-yl)-4-[(3-chloro-isoxazole-5-carbonyl)-amino]-2-hydroxy-pentanoic acid;
(bb)(2R,4R)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxy-4-[(3-isopropyl-isoxazole-5-carbonyl)-amino]-pentanoic acid;
(cc) (2R,4R)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxy-4-[(3-propyl-isoxazole-5-carbonyl)-amino]-pentanoic acid;
(dd)(2R,4R)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxy-4-[(3-isobutyl-isoxazole-5-carbonyl)-amino]-pentanoic acid;
(ee) (2R,4R)-5-(3′-Chloro-biphenyl-4-yl)-2-hydroxy-4-{[3-(1-hydroxy-1-methyl-ethyl)-isoxazole-5-carbonyl]-amino}-pentanoic acid;
(ff) (2R,4R)-4-[(3-tert-Butyl-isoxazole-5-carbonyl)-amino]-5-(3′-chloro-biphenyl-4-yl)-2-hydroxy-pentanoic acid;
(gg) (2R,4R)-5-(3′-Chlorobiphenyl-4-yl)-4-{[5-(2-chlorophenyl)-isoxazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid; and
(hh) (2R,4R)-5-(3′-Chlorobiphenyl-4-yl)-2-hydroxy-4-{[5-(2-hydroxyphenyl)-isoxazole-3-carbonyl]-amino}-pentanoic acid;
or a pharmaceutically acceptable salt thereof.
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