Substituted biphenyl derivatives

Abstract

Novel compounds which are 2,6-di-tertiary-butylphenols substituted in the 4 position by an acylaminophenyl group, which acylaminophenyl group is substituted by a moiety which includes a carboxyl group, are useful as inhibitors of leukotriene biosynthesis and as antiallergic agents.

What is claimed is: .[.1. A compound of the formula ##STR5## wherein L is divalent phenyl, straight-chained lower alkylene wherein the alkylene chain may optionally contain an ether or thioether linkage, or divalent cycloalkyl, with the proviso that when L is divalent cycloalkyl and the amide carbonyl and the carboxyl are on adjacent carbons, then the amide carbonyl and the carboxyl are cis to each other; or a carboxylate derivative thereof selected from a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid addition salt and a 
     
        pharmaceutically acceptable carboxylate salt..]. .[.2.  A compound of claim 1 wherein the ##STR6## 
     
     
        group is oriented para to the biphenyl bond..]. .[.3.  A method for inhibiting bronchoconstriction due to an allergic reaction in a mammal comprising administering a compound according to claim 1 to said mammal in 
     
     
        an amount effective to inhibit said constriction..]. .[.4.  An antiallergic pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, said compound being present in an amount sufficient for providing an antiallergic response..]. .[.5. A method for inhibiting leukotriene biosynthesis in a mammal comprising administering a compound according to claim 1 to said mammal in an amount effective to inhibit said synthesis..]. .Iadd.6. A method for inhibiting bronchoconstriction due to an allergic reaction in a mammal comprising administering to said mammal a compound of the formula ##STR7## wherein L is divalent phenyl, straight-chained lower alkylene wherein the alkylene chain may optionally contain an ether or thioether linkage, or divalent cycloalkyl, with the proviso that when L is divalent cycloalkyl and the amide carbonyl and the carboxyl are on adjacent carbons, then the amide carbonyl and the carboxyl are cis to each other; or a carboxylate derivative thereof selected from a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid addition salt and a pharmaceutically acceptable carboxylate salt, 
     
     
       in an amount effective to inhibit said constriction. .Iaddend. .Iadd.7.  A method for inhibiting leukotriene biosynthesis in a mammal comprising administering to said mammal a compound according of the formula ##STR8## wherein L is divalent phenyl, straight-chained lower alkylene wherein the alkylene chain may optionally contain an ether or thioether linkage, or divalent cycloalkyl, with the proviso that when L is divalent cycloalkyl and the amide carbonyl and the carboxyl are on adjacent carbons, then the amide carbonyl and the carboxyl are cis to each other; or a carboxylate derivative thereof selected from a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid addition salt and a pharmaceutically acceptable carboxylate salt, 
     
     
       in an amount effective to inhibit said synthesis. .Iaddend. .Iadd.8.  A compound selected from the group consisting of N-(3',5'-di-tertiary-butyl-4'-hydroxy-2-biphenylyl)glutaramic acid, N-(3',5'-di-tertiary-butyl-4'-hydroxy-2-biphenylyl)diglycolamic acid, 2-{N-[4-(3,5-di-t-butyl-4-hydroxyphenyl)-phenyl]carbamoyl}benzoic acid, cis-2-{N-[4-(3,5-di-t-butyl-4-hydroxyphenyl)phenyl]carbamyl}cyclohexanecarboxylic acid, and a carboxylate derivative thereof selected from the group consisting of a lower alkyl ester, a (lower) alkylamino(lower)alkyl ester, a pharmaceutically acceptable (lower)alkylamino (lower)alkyl ester acid-addition salt and a pharmaceutically acceptable carboxylate salt. 
     
     
        .Iaddend. .Iadd.9.  A method for inhibiting bronchoconstriction due to an allergic response in a mammal, comprising administering to said mammal a compound according to claim 8 in an amount effective to inhibit said constriction. .Iaddend. .Iadd.10. An antiallergic pharmaceutical composition, comprising a compound according to claim 8 and a pharmaceutically acceptable carrier, said compound being present in an amount sufficient for providing an antiallergic response. .Iaddend. 
     
     
        .Iadd. 1.  A method for inhibiting leukotriene biosynthesis in a mammal, comprising administering to said mammal a compound according to claim 8 in 
     
     
        an amount effective to inhibit said synthesis. .Iaddend. .Iadd.12.  An antiallergic pharmaceutical composition comprising a compound of the formula ##STR9## wherein L is divalent phenyl, straight-chained lower alkylene wherein the alkylene chain may optionally contain an ether or thioether linkage, or divalent cycloalkyl, with the proviso that when L is divalent cycloalkyl and the amide carbonyl and the carboxyl are on adjacent carbons, then the amide carbonyl and the carboxyl are cis to each other; or a carboxylate derivative thereof selected from a lower alkyl ester, a (lower)alkylamino(lower)alkyl ester, a pharmaceutically acceptable (lower)alkylamino(lower)alkyl ester acid addition salt and a pharmaceutically acceptable carboxylate salt, in a dosage form selected from the group consisting of a tablet, a capsule, an aerosol, a controlled release patch, and a powder, said compound being present in an amount sufficient for providing an antiallergic response.   
     
     
        .Iaddend. .Iadd.13.  An antiallergic pharmaceutical composition in a dosage form selected from the group consisting of a tablet, a capsule, an aerosol, a controlled release patch, and a powder, said dosage form comprising a compound according to claim 8, said compound being present in an amount sufficient for providing an antiallergic response. .Iaddend.