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ID: ALA1147577

Journal: Bioorg Med Chem Lett

Title: Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors incorporating substituted biphenyl P4 motifs.

Authors: Zhang P, Bao L, Zuckett JF, Goldman EA, Jia ZJ, Arfsten A, Edwards S, Sinha U, Hutchaleelaha A, Park G, Lambing JL, Hollenbach SJ, Scarborough RM, Zhu BY.

Abstract: Anthranilamides 4 and 5 were designed and synthesized as selective and orally bioavailable factor Xa inhibitors. Structural modifications aimed at lowering their lipophilicity were performed at the central phenyl ring and at the S4 binding biphenyl region by incorporating water solublizing substituents. The resulting compounds (e.g., 7, 8, 14, 30a, and 32b) are highly potent in vitro, and show improved activity in human plasma-based thrombin generation assay.

CiteXplore: 15013006

DOI: 10.1016/j.bmcl.2003.11.079