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ID: ALA1153173

Journal: Bioorg Med Chem Lett

Title: Oxygenated analogues of UK-396082 as inhibitors of activated thrombin activatable fibrinolysis inhibitor.

Authors: Owen DR, Bull DJ, Bunnage ME, Glossop MS, Maguire RJ, Strang RS.

Abstract: A suitable inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa) has the potential to be a novel treatment for thrombosis. The TAFIa inhibitor UK-396082 (1) was used as a starting point to seek more potent analogues. With knowledge of encouraging human pharmacokinetics and toleration for the clinical candidate (1), the programme continued to seek structure-activity relationships (SAR) that could positively impact on both potency and half-life, and therefore the projected dose of any future nominated clinical agent. A series of oxygenated analogues based on compound 1 were prepared to evaluate changes in pharmacology, selectivity and pharmacokinetics.

CiteXplore: 19954973

DOI: 10.1016/j.bmcl.2009.11.029