title: Orally bioavailable factor Xa inhibitors containing alpha-substituted gem-dimethyl P4 moieties.
abstract: In an effort to identify a potential back-up to apixaban (Eliquis®), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent FXa binding affinity (FXa Ki), good human plasma anticoagulant activity (PT EC2x), cell permeability, and oral bioavailability.
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. Electronic address: michael.orwat@bms.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Orwat
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Jennifer X
authors.initials: JX
authors.lastname: Qiao
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Rendina
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Baomin
authors.initials: B
authors.lastname: Xin
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Knabb
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Patrick Y S
authors.initials: PY
authors.lastname: Lam
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Donald J P
authors.initials: DJ
authors.lastname: Pinto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002463:Cell Membrane Permeability / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D015951:Factor Xa
keywords: Factor Xa inhibitors; Thromboembolic disorders