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ID: ALA1132849

Journal: Bioorg Med Chem Lett

Title: Amidinohydrazones as guanidine bioisosteres: application to a new class of potent, selective and orally bioavailable, non-amide-based small-molecule thrombin inhibitors.

Authors: Soll RM, Lu T, Tomczuk B, Illig CR, Fedde C, Eisennagel S, Bone R, Murphy L, Spurlino J, Salemme FR.

Abstract: We describe a new class of potent, non-amide-based small molecule thrombin inhibitors in which an amidinohydrazone is used as a guanidine bioisostere on a non-peptide scaffold. Compound 4 exhibits nM inhibition of thrombin, is selective for thrombin, and shows 60 and 23% bioavailability in rabbits and dogs, respectively. Crystallographic analysis of 4 bound to thrombin confirmed the amindinohydrazone binding mode.

CiteXplore: 10636229

DOI: 10.1016/s0960-894x(99)00632-0