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.
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.
Marlowe
C K
CK
COR Therapeutics, Inc., South San Francisco, CA 94080, USA.
Sinha
U
U
Gunn
A C
AC
Scarborough
R M
RM
D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D065427:Factor Xa Inhibitors; D005563:Formic Acid Esters / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013925:Thromboplastin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005563:Formic Acid Esters; D009842:Oligopeptides; C033879:argininal; C000345:t-butyloxycarbonyl group; D013925:Thromboplastin; D001120:Arginine; D005998:Glycine