title: Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa.
abstract: A series of functionalized aryl boronic acids were synthesized and evaluated as potential inhibitors of factor XIa. Crystal structures of the protein-inhibitor complexes led to the design and synthesis of second generation compounds showing single digit micromolar inhibition against FXIa and selectivity against thrombin, trypsin, and FXa.
authors.affiliation: Medicinal Chemistry, Daiichi Asubio Medical Research Laboratories, LLC, One Kendall Square, Building 700, Cambridge, MA 02139, USA. tlazarova@medchempartners.com
authors.forename: Tsvetelina I
authors.initials: TI
authors.lastname: Lazarova
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Michael
authors.initials: M
authors.lastname: Rynkiewicz
authors.forename: Joan C
authors.initials: JC
authors.lastname: Gorga
authors.forename: Frank
authors.initials: F
authors.lastname: Bibbins
authors.forename: Harold V
authors.initials: HV
authors.lastname: Meyers
authors.forename: Robert
authors.initials: R
authors.lastname: Babine
authors.forename: James
authors.initials: J
authors.lastname: Strickler
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000925:Anticoagulants; D001897:Boronic Acids; D015842:Serine Proteinase Inhibitors; D015945:Factor XIa