title: Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.
abstract: The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to be the best compound in this series (FXa Ki = 0.35 nM) based on potency, selectivity, and pharmacokinetic profile.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. jennifer.qiao@bms.com
authors.forename: Jennifer X
authors.initials: JX
authors.lastname: Qiao
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cheng
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Smallheer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Galemmo
authors.forename: Spencer
authors.initials: S
authors.lastname: Drummond
authors.forename: Donald J P
authors.initials: DJ
authors.lastname: Pinto
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.forename: Pancras C
authors.initials: PC
authors.lastname: Wong
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
mesh_terms: D000818:Animals; D004285:Dogs; D065427:Factor Xa Inhibitors; D008958:Models, Molecular; D010880:Piperidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011485:Protein Binding; D011720:Pyrazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
chemical_list: D065427:Factor Xa Inhibitors; D010880:Piperidines; D011720:Pyrazoles