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ID: ALA1136169

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of potent and selective macrocyclic thrombin inhibitors.

Authors: Nantermet PG, Barrow JC, Newton CL, Pellicore JM, Young M, Lewis SD, Lucas BJ, Krueger JA, McMasters DR, Yan Y, Kuo LC, Vacca JP, Selnick HG.

Abstract: A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

CiteXplore: 12873514

DOI: 10.1016/s0960-894x(03)00506-7