Solution-phase combinatorial synthesis of nonpeptide bradykinin antagonists.
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.
Kam
Yoo Lim
YL
School of Pharmacy, Ewha Womans University, Seoul 120-750, South Korea.
Rhee
Soo-Jin
SJ
Choo
Hea-Young P
HY
D000586:Amination; D000818:Animals; D065168:Bradykinin Receptor Antagonists; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007098:Imino Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry; D018002:Receptors, Bradykinin / Q000737:chemistry / Q000378:metabolism; D012996:Solutions / Q000737:chemistry
D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D007098:Imino Acids; D011804:Quinolines; D018002:Receptors, Bradykinin; D012996:Solutions; C008109:iminodiacetic acid