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ID: ALA1136607

Journal: Bioorg Med Chem Lett

Title: Novel thrombin inhibitors incorporating non-basic partially saturated heterobicyclic P1-arginine mimetics.

Authors: Peterlin-Masic L, Mlinsek G, Solmajer T, Trampus-Bakija A, Stegnar M, Kikelj D.

Abstract: 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.

CiteXplore: 12617892

DOI: 10.1016/s0960-894x(03)00030-1