Solution-phase combinatorial synthesis of nonpeptide bradykinin antagonists

Abstract

We describe the solution-phase combinatorial synthesis and pharmacological effect of fifty N,N′-substituted-N″-1-(4- chlorobenzhydryl)piperazine iminodiacetic acid triamide derivatives as nonpeptide B2 antagonists. The synthesized compounds were tested for their antibradykinin activity by utilizing guinea-pig ileum smooth muscle. Most of the compounds showed antagonistic effects on bradykinin induced contraction. N-acetyl-N′-(4-methylbenzyl)-N″-1-(4-chlorobenzhydryl) piperazine iminodiacetic acid triamide (A3B1C1) showed the 46% inhibition at 100nM. © 2004 Elsevier Ltd. All rights reserved.