Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold.
Basic Information
ID: ALA2417432
Journal: Bioorg Med Chem Lett
Title: Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold.
Authors: Bolton SA, Sutton JC, Anumula R, Bisacchi GS, Jacobson B, Slusarchyk WA, Treuner UD, Wu SC, Zhao G, Pi Z, Sheriff S, Smirk RA, Bisaha S, Cheney DL, Wei A, Schumacher WA, Hartl KS, Liu E, Zahler R, Seiler SM.
Abstract: In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIIa inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIIa is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor VIIa.
CiteXplore: 23927973
DOI: 10.1016/j.bmcl.2013.06.028
Patent ID: ┄