Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa.
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.
Lazarova
Tsvetelina I
TI
Medicinal Chemistry, Daiichi Asubio Medical Research Laboratories, LLC, One Kendall Square, Building 700, Cambridge, MA 02139, USA. tlazarova@medchempartners.com
Jin
Lei
L
Rynkiewicz
Michael
M
Gorga
Joan C
JC
Bibbins
Frank
F
Meyers
Harold V
HV
Babine
Robert
R
Strickler
James
J
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
D000925:Anticoagulants; D001897:Boronic Acids; D015842:Serine Proteinase Inhibitors; D015945:Factor XIa