Case History
作者： Donald J.P. Pinto , Pancras C. Wong , Robert M. Knabb , Ruth R. Wexler
DOI: 10.1016/B978-0-12-396492-2.00009-6
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摘要: Abstract Eliquis™ (apixaban) is the culmination of an intense medicinal chemistry effort to identify a highly optimized inhibitor coagulation factor Xa (FXa). We sought safe and efficacious FXa with high oral bioavailability suitable for twice daily (BID) or once (QD) dosing low peak/trough ratio minimize potential bleeding liabilities. During lead optimization phase, computer-aided drug design X-ray crystallography were leveraged drive affinity selectivity by capitalizing on larger S1 pocket FXa. Oral was achieved driving picomolar range followed replacing positively charged P1 group neutral group. Apixaban meets all criteria set ideal anticoagulant favorable PK safety profile, bioavailability, minimum ratio. In clinical trials, apixaban shown be effective in VTE prevention AF trials.
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