Design, synthesis and structure-activity relationship of a series of arginine aldehyde factor Xa inhibitors. Part 1: structures based on the (D)-Arg-Gly-Arg tripeptide sequence

C K Marlowe; U Sinha; A C Gunn; R M Scarborough

doi:10.1016/s0960-894x(99)00582-x

Design, synthesis and structure-activity relationship of a series of arginine aldehyde factor Xa inhibitors. Part 1: structures based on the (D)-Arg-Gly-Arg tripeptide sequence

Bioorg Med Chem Lett. 2000 Jan 3;10(1):13-6. doi: 10.1016/s0960-894x(99)00582-x.

Authors

C K Marlowe¹, U Sinha, A C Gunn, R M Scarborough

Affiliation

¹ COR Therapeutics, Inc., South San Francisco, CA 94080, USA.

PMID: 10636232
DOI: 10.1016/s0960-894x(99)00582-x

Abstract

A series of arginine aldehyde inhibitors was designed as transition state (TS) analogues based on the known factor Xa specific substrate Cbz-D-Arg-Gly-Arg-pNA. BnSO2-(D)Arg-Gly-Arg-H (20) was found to be the most potent and selective inhibitor of factor Xa and prothrombinase activity in this series.

MeSH terms

Anticoagulants / chemical synthesis*
Anticoagulants / pharmacology*
Arginine / analogs & derivatives*
Arginine / chemical synthesis
Arginine / chemistry
Arginine / pharmacology
Drug Design
Factor Xa Inhibitors*
Formic Acid Esters / chemistry
Glycine / analogs & derivatives*
Glycine / chemistry
Oligopeptides / chemical synthesis*
Oligopeptides / pharmacology*
Structure-Activity Relationship
Substrate Specificity
Thromboplastin / antagonists & inhibitors

Substances

Anticoagulants
Factor Xa Inhibitors
Formic Acid Esters
Oligopeptides
argininal
t-butyloxycarbonyl group
Thromboplastin
Arginine
Glycine