Dual-acting antihypertensive agents

Abstract

The invention is directed to compounds of formula I: wherein Ar, r, R 3 , X, and R 5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT 1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.

1 - 36 . (canceled) 
     
     
         37 . A method for treating hypertension, comprising administering to a patient a therapeutically effective amount of a compound having both AT 1  receptor-antagonizing activity and neprilysin enzyme-inhibiting activity. 
     
     
         38 . The method of  claim 37 , wherein the compound has a pK i  value for binding to an AT 1  receptor greater than or equal to about 5.0 and a pIC 50  value for the inhibition of the neprilysin enzyme greater than or equal to about 5.0. 
     
     
         39 . The method of  claim 38 , wherein the compound has a pK i  value greater than or equal to about 6.0. 
     
     
         40 . The method of  claim 39 , wherein the compound has a pK i  value within the range of about 8.0-10.0. 
     
     
         41 . The method of  claim 38 , wherein the compound has a pIC 50  value greater than or equal to about 6.0. 
     
     
         42 . The method of  claim 41 , wherein the compound has a pIC 50  value within the range of about 7.0-10.0. 
     
     
         43 . (canceled) 
     
     
         44 . A method for treating heart failure, comprising administering to a patient a therapeutically effective amount of a compound having both AT 1  receptor-antagonizing activity and NEP enzyme-inhibiting activity. 
     
     
         45 . The method of  claim 44 , wherein the compound has a pK i  value for binding to an AT 1  receptor greater than or equal to about 5.0 and a pIC 50  value for the inhibition of the neprilysin enzyme greater than or equal to about 5.0. 
     
     
         46 . (canceled) 
     
     
         47 . A method of treating a patient suffering from a disease or disorder that is treated by antagonizing the AT 1  receptor and/or inhibiting the NEP enzyme, comprising administering to a patient a therapeutically effective amount of a compound having both AT 1  receptor-antagonizing activity and NEP enzyme-inhibiting activity. 
     
     
         48 . The method of  claim 47 , wherein the compound has a pK i  value for binding to an AT 1  receptor greater than or equal to about 5.0 and a pIC 50  value for the inhibition of the neprilysin enzyme greater than or equal to about 5.0. 
     
     
         49 - 54 . (canceled)