Neprilysin inhibitors

Abstract

In one aspect, the invention relates to compounds having the formula: where R 1 , R 2 , R 3 , X, R 4 , R 5 , and R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

1 - 22 . (canceled) 
     
     
         23 : A compound of:
 (a) (2R,3R)-3-{[3-(6-bromo-pyridin-3-ylmethyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carbonyl]-amino}-2-hydroxy-4-phenyl-butyric acid;   (b) (2R,3R)-2-hydroxy-3-[(7-methyl-2-propyl-3-pyridin-3-ylmethyl-3H-benzoimidazole-5-carbonyl)-amino]-4-phenyl-butyric acid;   (c) (2R,3R)-2-hydroxy-3-[(7-methyl-2-propyl-3-pyridin-3-ylmethyl-3H-benzoimidazole-5-carbonyl)-amino]-4-phenyl-butyric acid ethyl ester;   (d) (2R,3R)-3-[(3-carboxymethyl-7-methyl-2-propyl-3H-benzoimidazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid;   (e) (2R,3R)-2-hydroxy-3-{[3-(2-methoxy-benzyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carbonyl]-amino}-4-phenyl-butyric acid;   (f) (2R,3R)-2-hydroxy-3-{[3-(4-methoxy-benzyl)-7-methyl-2-propyl-3H-benzoimidazole-5-carbonyl]-amino}-4-phenyl-butyric acid;   (g) (2R,3R)-3-[(3-carbamoylmethyl-7-methyl-2-propyl-3H-benzoimidazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid;   (h) (2R,3R)-3-[(7-chloro-2-ethyl-3H-benzoimidazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid;   (i) (2R,3R)-3-[(7-chloro-2-ethyl-1H-benzoimidazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid ethyl ester;   (j) (2R,3R)-3-[(3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid;   (k) (2R,3R)-3-[(3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid ethyl ester;   (l) (2R,3R)-3-[(7-chloro-3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid;   (m) (2R,3R)-3-[(7-chloro-3H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid ethyl ester;   (n) (2R,3R)-2-hydroxy-3-[(7-methyl-3H-benzotriazole-5-carbonyl)-amino]-4-phenyl-butyric acid;   (o) (2R,3R)-3-[(7-fluoro-1H-benzotriazole-5-carbonyl)-amino]-2-hydroxy-4-phenyl-butyric acid; or
 a pharmaceutically acceptable salt thereof. 
   
     
     
         24 : A pharmaceutical composition comprising the compound of  claim 23  and a pharmaceutically acceptable carrier. 
     
     
         25 : The pharmaceutical composition of  claim 24 , further comprising an AT 1  receptor antagonist. 
     
     
         26 : A method for treating hypertension, heart failure, or renal disease, comprising administering to a patient a therapeutically effective amount of the compound of  claim 23 .