Publication Abstract from PubMed
A series of 4,5,6,7-tetrahydro-1H-benzimidazole-5-carboxylic acid and 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid derivatives designed as inhibitors of TAFIa has been prepared via a common hydrogenation-alkylation sequence starting from the appropriate benzimidazole and imidazopyridine system. We present a successful design strategy using a conformational restriction approach resulting in potent and selective inhibitors of TAFIa. The X-ray structure of compound 5 in complex with a H333Y/H335Q double mutant TAFI indicate that the conformational restriction is responsible for the observed potency increase.
Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa).,Brink M, Dahlen A, Olsson T, Polla M, Svensson T Bioorg Med Chem. 2014 Apr 1;22(7):2261-8. doi: 10.1016/j.bmc.2014.02.010. Epub, 2014 Feb 18. PMID:24588961[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
