Development of Potent and Selective Plasmin and Plasma Kallikrein Inhibitors and Studies on the Structure-Activity Relationship

Yoshio OKADA; Yuko TSUDA; Mayako TADA; Keiko WANAKA; Utako OKAMOTO; Akiko HIJIKATA-OKUNOMIYA; Shosuke OKAMOTO

doi:10.1248/cpb.48.1964

Yoshio OKADA, Yuko TSUDA, Mayako TADA, Keiko WANAKA, Utako OKAMOTO, Akiko HIJIKATA-OKUNOMIYA, Shosuke OKAMOTO

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Keywords: plasmin inhibitor, plasma kallikrein inhibitor, selectivity, structure-activity relationship

JOURNAL FREE ACCESS

2000 Volume 48 Issue 12 Pages 1964-1972

DOI https://doi.org/10.1248/cpb.48.1964

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Abstract

Based on structure-activity relationship studies, we designed and synthesized plasmin (PL) and plasma Kallikrein (PK) inhibitors. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-Pic)-octylamide inhibited PL, PK, urokinase (UK) and thrombin (TH) with IC₅₀ values of 0.53, 30 5.3 and >400μM, respectively. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-Pyrim)-4-carboxyanilide inhibited PL, PK, UK and TH with IC₅₀ values of 36, 0.56, 440 and >1000μM, respectively.

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