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ID: ALA1135152

Journal: Bioorg Med Chem Lett

Title: Design, synthesis, and SAR of monobenzamidines and aminoisoquinolines as factor Xa inhibitors.

Authors: Zhang P, Zuckett JF, Woolfrey J, Tran K, Huang B, Wong P, Sinha U, Park G, Reed A, Malinowski J, Hollenbach S, Scarborough RM, Zhu BY.

Abstract: Monoamidine FXa inhibitors 3 were designed and synthesized. SAR studies and molecular modeling led to the design of conformationally constrained diaryl ethers 4 and 5, as well as benzopyrrolidinone 7 as potent FXa inhibitors. The monoamidines show high efficacy in a DVT model, but lack desirable oral bioavailability. The benzopyrrolidinone-based aminoisoquinolines 8 do not show significant improvement in oral bioavailability.

CiteXplore: 12039584

DOI: 10.1016/s0960-894x(02)00234-2