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ID: ALA1921766

Journal: Bioorg Med Chem Lett

Title: Orally active zwitterionic factor Xa inhibitors with long duration of action.

Authors: Mochizuki A, Nagata T, Kanno H, Takano D, Kishida M, Suzuki M, Ohta T.

Abstract: We have optimized 2-aminomethylphenylamine derivative as a factor Xa inhibitor. Several polar functional groups were introduced in the central phenyl ring, and we focused on zwitter ionic compound showing continuous inhibitory activity in oral administration test. In vitro and oral activities were improved by optimization of S1 and S4 ligands. Incorporating the interaction with S1-β pocket enhanced in vitro factor Xa inhibitory activity to less than 1 nM. Many zwitter ionic compounds showed long duration of action and potent inhibitory activity and high AUC values in oral administration tests to monkeys.

CiteXplore: 22044620

DOI: 10.1016/j.bmcl.2011.10.021