title: Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally bioavailable factor Xa inhibitors.
abstract: We have previously reported on a series of aminobenzisoxazoles as potent, selective, and orally bioavailable factor Xa inhibitors, which culminated in the discovery of razaxaban. Herein, we describe another approach to improve factor Xa inhibitory potency and pharmacokinetic profile by incorporating basic and water soluble functionalities on the terminal ring of the P4 biaryl group found in our earlier Xa inhibitors. This approach resulted in a series of potent, selective, and orally bioavailable factor Xa inhibitors.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. mimi.quan@bms.com
authors.forename: Mimi L
authors.initials: ML
authors.lastname: Quan
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.forename: John M
authors.initials: JM
authors.lastname: Fevig
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
authors.forename: Steve
authors.initials: S
authors.lastname: Bai
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.forename: Pancras C
authors.initials: PC
authors.lastname: Wong
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
mesh_terms: D000284:Administration, Oral; D001583:Benzoxazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001583:Benzoxazoles; D065427:Factor Xa Inhibitors; D015842:Serine Proteinase Inhibitors