Neprilysin inhibitors

Abstract

In one aspect, the invention relates to compounds having the formula I: where R 1 , R 2a , R 2b , and R 3 -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 these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

1 - 25 . (canceled) 
     
     
         26 : A compound of:
 (a) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-2-methyl-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid or a pharmaceutically acceptable salt thereof;   (b) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-4-[(2-cyclopropyloxazole-4-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;   (c) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-4-[(5-chloropyridine-2-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;   (d) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-2-methyl-4-[(pyrimidine-2-carbonyl)amino]pentanoic acid;   (e) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-2-methyl-4-[(5-trifluoromethylpyridine-2-carbonyl)amino]pentanoic acid;   (f) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-2-methyl-4-[(oxazole-2-carbonyl)amino]pentanoic acid;   (g) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-2-methyl-4-[(1H-[1,2,4]triazole-3-carbonyl)amino]pentanoic acid;   (h) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-4-[(1-ethoxy-1H-[1,2,3]triazole-4-carbonyl)amino]-2-methoxymethyl-2-methylpentanoic acid;   (i) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-2-methoxymethyl-4-[(1-methoxy-1H-[1,2,3]triazole-4-carbonyl)amino]-2-methylpentanoic acid;   (j) (2S,4R)-5-(5′-Chloro-2′-fluorobiphenyl-4-yl)-4-{[1-(2-hydroxyethyl)-1H-[1,2,3]triazole-4-carbonyl]amino}-2-methoxymethyl-2-methylpentanoic acid; or a pharmaceutically acceptable salt thereof.   
     
     
         27 : A pharmaceutical composition comprising the compound of  claim 26  and a pharmaceutically acceptable carrier. 
     
     
         28 : The pharmaceutical composition of  claim 27 , further comprising an AT 1  receptor antagonist. 
     
     
         29 : A method for treating hypertension, heart failure, or renal disease, comprising administering to a patient a therapeutically effective amount of the compound of  claim 26 .