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Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.

Abstract：

:Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Young RJ,Campbell M,Borthwick AD,Brown D,Burns-Kurtis CL,Chan C,Convery MA,Crowe MC,Dayal S,Diallo H,Kelly HA,King NP,Kleanthous S,Mason AM,Mordaunt JE,Patel C,Pateman AJ,Senger S,Shah GP,Smith PW,Watson NS,West

doi

10.1016/j.bmcl.2006.09.001

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

5953-7

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(06)01047-X

journal_volume

16

pub_type

杂志文章

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