Document Report Card

ID: ALA3576790

Journal: J Med Chem

Title: Novel Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) from Natural Product Anabaenopeptin.

Authors: Halland N, Brönstrup M, Czech J, Czechtizky W, Evers A, Follmann M, Kohlmann M, Schiell M, Kurz M, Schreuder HA, Kallus C.

Abstract: Anabaenopeptins isolated from cyanobacteria were identified as inhibitors of carboxypeptidase TAFIa. Cocrystal structures of these macrocyclic natural product inhibitors in a modified porcine carboxypeptidase B revealed their binding mode and provided the basis for the rational design of small molecule inhibitors with a previously unknown central urea motif. Optimization based on these design concepts allowed for a rapid evaluation of the SAR and delivered potent small molecule inhibitors of TAFIa with a promising overall profile.

CiteXplore: 25990761

DOI: 10.1021/jm501840b