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Bioorg Med Chem Lett. 2006 Dec 1;16(23):5953-7. Epub 2006 Sep 18.

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

Author information

1
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Rob.J.Young@gsk.com <Rob.J.Young@gsk.com>

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.

PMID:
16982190
DOI:
10.1016/j.bmcl.2006.09.001
[Indexed for MEDLINE]

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