title: Benzylamine-based selective and orally bioavailable inhibitors of thrombin.
abstract: A series of p-aminomethylphenylalanine derivatives were investigated as novel thrombin inhibitors. This study led to potent inhibitors of thrombin (Ki up to 3.3 nM) that are trypsin-selective, highly orally bioavailable in rats, and highly permeable across Caco-2 cells. The P1 benzylamine binding mode in the thrombin active site was identified by X-ray crystallographic analysis.
authors.affiliation: Biotech Research Institute, LG Chemical Ltd./Research Park, Taejon, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: W H
authors.initials: WH
authors.lastname: Jung
authors.forename: C W
authors.initials: CW
authors.lastname: Park
authors.forename: C Y
authors.initials: CY
authors.lastname: Hong
authors.forename: I C
authors.initials: IC
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Oh
authors.forename: O H
authors.initials: OH
authors.lastname: Kwon
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: H D
authors.initials: HD
authors.lastname: Park
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000737:chemistry*; D001682:Biological Availability; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D001596:Benzylamines; D015842:Serine Proteinase Inhibitors; C030796:benzylamine; D013917:Thrombin