Neprilysin inhibitors

Abstract

In one aspect, the invention relates to compounds having the formula: where R 1 , R 2a , R 2b , R 3 -R 6 , a, b, Z, and X 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 processes and intermediates for preparing such compounds.

1 - 29 . (canceled) 
     
     
         30 : A compound selected from:
 (a) 3-[N-biphenyl-4-ylmethyl-N′-(3-hydroxy-isoxazole-5-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid ethyl ester;   (b) 3-[N-biphenyl-4-ylmethyl-N′-(3-hydroxy-isoxazole-5-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (c) 3-[N-biphenyl-4-ylmethyl-N′-(3H-[1,2,3]triazole-4-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (d) 3-[N-biphenyl-4-ylmethyl-N′-(5-chloro-4H-[1,2,4]triazole-3-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (e) 3-[N-biphenyl-4-ylmethyl-N′-(3-methoxy-isoxazole-5-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (f) 3-[N-biphenyl-4-ylmethyl-N′-(2-hydroxy-pyrimidine-5-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (g) 3-[N-biphenyl-4-ylmethyl-N′-(5-hydroxy-2H-pyrazole-3-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid;   (h) 5-[N′-biphenyl-4-ylmethyl-N′-(2-carboxy-2-hydroxy-propyl)-hydrazinocarbonyl]-1H-pyrazole-3-carboxylic acid;   (i) 3-[N-biphenyl-4-ylmethyl-N′-(5-dimethylcarbamoyl-2H-pyrazole-3-carbonyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid; and   (j) 3-{N-biphenyl-4-ylmethyl-N′-[5-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-hydrazino}-2-hydroxy-2-methyl-propionic acid;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         31 : A pharmaceutical composition comprising the compound of  claim 30  and a pharmaceutically acceptable carrier. 
     
     
         32 : The pharmaceutical composition of  claim 31 , further comprising an AT 1  receptor antagonist. 
     
     
         33 : A method for therapeutically treating hypertension, heart failure, or renal disease, comprising administering to a patient a therapeutically effective amount of the compound of  claim 30 .