Synthesis, SAR exploration, and X-ray crystal structures of factor XIa inhibitors containing an alpha-ketothiazole arginine.
Using an alpha-ketothiazole arginine moiety as a key recognition element, a series of small peptidomimetic molecules was designed and synthesized, and their co-crystal structures with factor XIa were studied in an effort to develop smaller, less peptidic inhibitors as antithrombotic agents.
Deng
Hongfeng
H
Department of Medicinal Chemistry, Daiichi Asubio Medical Research Laboratories, LLC (DAIAMED), One Kendall Square, Bldg 700, Cambridge, MA 02139, USA. hongfeng.deng@praecis.com
Bannister
Thomas D
TD
Jin
Lei
L
Babine
Robert E
RE
Quinn
Jesse
J
Nagafuji
Pamela
P
Celatka
Cassandra A
CA
Lin
Jian
J
Lazarova
Tsvetelina I
TI
Rynkiewicz
Michael J
MJ
Bibbins
Frank
F
Pandey
Pramod
P
Gorga
Joan
J
Meyers
Harold V
HV
Abdel-Meguid
Sherin S
SS
Strickler
James E
JE
D000577:Amides / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000577:Amides; D013844:Thiazoles; C481397:alpha-ketothiazole; D001120:Arginine; D015945:Factor XIa