Development of potent and selective plasmin and plasma kallikrein inhibitors and studies on the structure-activity relationship

Authors
Okada, Y Tsuda, Y Tada, M Wanaka, K Okamoto, U Hijikata-Okunomiya, A Okamoto, S
Citation
Y. Okada et al., Development of potent and selective plasmin and plasma kallikrein inhibitors and studies on the structure-activity relationship, CHEM PHARM, 48(12), 2000, pp. 1964-1972
Citations number
30
Categorie Soggetti
Chemistry & Analysis
Journal title
CHEMICAL & PHARMACEUTICAL BULLETIN
ISSN journal
00092363 → ACNP
Volume
48
Issue
12
Year of publication
2000
Pages
1964 - 1972
Database
ISI
SICI code
0009-2363(200012)48:12<1964:DOPASP>2.0.ZU;2-Q
Abstract
Based on structure-activity relationship studies, we designed and synthesiz ed plasmin (PL) and plasma kallikrein (PK) inhibitors. Trans-(4-aminomethyl cyclohesanecarbonyl)-Tyr( O-Pic)-octylamide inhibited PL, PK, urokinase (UK ) and thrombin (TH) with IC50 values of 0.53, 30, 5.3 and >400 muM, respect ively: Trans-(4-amino methylcyclohesanecarbonyl)-Tyr(O-2-Pyrim)-4-carboxyan ilide inhibited PL, PK, UK and TH with IC50 values of 36, 0.56, 430 and >10 00 muM, respectively.