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ID: ALA1135946

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P(1) structure-activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides.

Authors: Jia ZJ, Wu Y, Huang W, Goldman E, Zhang P, Woolfrey J, Wong P, Huang B, Sinha U, Park G, Reed A, Scarborough RM, Zhu BY.

Abstract: Based on DuPont Pharmaceuticals' monobenzamidine lead structure SN429, we have designed the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as a novel series of non-basic factor Xa inhibitors. We have discovered that the displacement of the benzamidine moiety with substituted 2-naphthyl structures not only results in highly potent factor Xa inhibitors, but also significantly increases their enzyme specificity and oral bioavailability.

CiteXplore: 12039583

DOI: 10.1016/s0960-894x(02)00239-1