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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

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

doi

10.1016/j.bmcl.2011.10.021

subject

Has Abstract

pub_date

2011-12-15 00:00:00

pages

7337-43

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01409-0

journal_volume

21

pub_type

杂志文章

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