title: Pyridine and pyridinone-based factor XIa inhibitors.
abstract: The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (±)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States. Electronic address: james.corte@bms.com.
authors.forename: James R
authors.initials: JR
authors.lastname: Corte
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Tianan
authors.initials: T
authors.lastname: Fang
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Hangeland
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Friends
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Rendina
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luettgen
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bozarth
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Barbera
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Anzhi
authors.initials: A
authors.lastname: Wei
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Vidhyashankar
authors.initials: V
authors.lastname: Ramamurthy
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Morin
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Dietmar A
authors.initials: DA
authors.lastname: Seiffert
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.affiliation: Discovery Chemistry and Cardiovascular Biology, Research and Development, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
authors.forename: Mimi L
authors.initials: ML
authors.lastname: Quan
mesh_terms: D018360:Crystallography, X-Ray; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011725:Pyridines / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011725:Pyridines; D011728:Pyridones; D015945:Factor XIa
keywords: Activated partial thromboplastin time; FXIa; Factor XIa inhibitors; Thrombosis; aPTT