Patent ID: 6423727
Filing Date: 2002-07-23
Classification: A61K,C07D

Abstract:
A method of inhibiting endothelin converting enzyme in a mammal which comprises administering to a mammal in need thereof an effective endothelin converting enzyme inhibiting amount of a compound of the formula. whereinR represents bicyclic carbocyclic aryl or bicyclic heterocyclic aryl; or a wholly or partially saturated form thereof; or R represents monocyclic carbocyclic aryl substituted by carbocyclic aryl or by heterocyclic aryl; or R represents monocyclic carbocyclic aryl substituted by cycloalkyl; or R represents monocyclic carbocyclic aryl substituted by azacycloalkyl which is optionally substituted by lower alkyl or acyl; or R represents cycloalkyl substituted by cycloalkyl or azacycloalkyl; R1 represents hydrogen or acyl; R2 represents hydrogen, lower alkyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, biaryl, biaryl-lower alkyl, (hydroxy, lower alkoxy or acyloxy)-lower alkyl, or lower alkyl-(thio, sulfinyl or sulfonyl)-lower alkyl; R3 represents hydrogen or lower alkyl; or R2 and R3 together with the carbon atom to which they are attached represent cycloalkylidene or benzo-fused cycloalkylidene; A together with the carbon atom to which it is attached forms a ring and represents 3 to 10 membered cycloalkylidene or 5 to 10 membered cycloalkenylidene radical which may be substituted by lower alkyl or aryl-lower alkyl or may be fused to a saturated or unsaturated carbocyclic 5-7-membered ring; or A together with the carbon to which it is attached represents 5 to 6 membered oxacycloalkylidene, thiacycloalkylidene or azacycloalkylidene optionally substituted by lower alkyl or aryl-lower alkyl; or A together with the carbon atom to which it is attached represents 2,2-norbonylidene; m is zero or 1-3; Y represents 5-tetrazolyl, carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester; a disulfide derivative derived from a said compound wherein R1 is hydrogen; or a pharmaceutically acceptable salt thereof.