title: Synthesis, SAR exploration, and X-ray crystal structures of factor XIa inhibitors containing an alpha-ketothiazole arginine.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Daiichi Asubio Medical Research Laboratories, LLC (DAIAMED), One Kendall Square, Bldg 700, Cambridge, MA 02139, USA. hongfeng.deng@praecis.com
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Deng
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bannister
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Babine
authors.forename: Jesse
authors.initials: J
authors.lastname: Quinn
authors.forename: Pamela
authors.initials: P
authors.lastname: Nagafuji
authors.forename: Cassandra A
authors.initials: CA
authors.lastname: Celatka
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Tsvetelina I
authors.initials: TI
authors.lastname: Lazarova
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rynkiewicz
authors.forename: Frank
authors.initials: F
authors.lastname: Bibbins
authors.forename: Pramod
authors.initials: P
authors.lastname: Pandey
authors.forename: Joan
authors.initials: J
authors.lastname: Gorga
authors.forename: Harold V
authors.initials: HV
authors.lastname: Meyers
authors.forename: Sherin S
authors.initials: SS
authors.lastname: Abdel-Meguid
authors.forename: James E
authors.initials: JE
authors.lastname: Strickler
mesh_terms: 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*
chemical_list: D000577:Amides; D013844:Thiazoles; C481397:alpha-ketothiazole; D001120:Arginine; D015945:Factor XIa