Novel thrombin inhibitors incorporating non-basic partially saturated heterobicyclic P1-arginine mimetics.
作者信息
Peterlin-Masic Lucija, Mlinsek Gregor, Solmajer Tomaz, Trampus-Bakija Alenka, Stegnar Mojca, Kikelj Danijel
机构信息
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
出版信息
Bioorg Med Chem Lett. 2003 Mar 10;13(5):789-94. doi: 10.1016/s0960-894x(03)00030-1.
The design, synthesis and biological activity of non-covalent thrombin inhibitors incorporating 4,5,6,7-tetrahydroindazole, 2-methyl-4,5,6,7-tetrahydroindazole, 4,5,6,7-tetrahydroisoindole, 5,6,7,8-tetrahydroquinazoline and 5,6,7,8-tetrahydroquinazolin-2-amine as novel, partially saturated, heterobicyclic P(1)-arginine side-chain mimetics is described. The binding mode of the most potent candidate in the series co-crystallized with human alpha-thrombin, which exhibited an in vitro K(i) of 140nM and more that 478-fold selectivity against trypsin, is discussed.
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