Structure-activity relationships of anthranilamide-based factor Xa inhibitors containing piperidinone and pyridinone P4 moieties.
Introduction of the phenyl piperidinone and phenyl pyridinone P4 moieties in the anthranilamide scaffold led to potent, selective, and orally bioavailable inhibitors of factor Xa. Anthranilamide 28 displayed comparable efficacy to apixaban in the rabbit arteriovenous-shunt (AV) thrombosis model.
Corte
James R
JR
Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543, USA. james.corte@bms.com
Fang
Tianan
T
Pinto
Donald J P
DJ
Han
Wei
W
Hu
Zilun
Z
Jiang
Xiang-Jun
XJ
Li
Yun-Long
YL
Gauuan
Jolicia F
JF
Hadden
Mark
M
Orton
Darren
D
Rendina
Alan R
AR
Luettgen
Joseph M
JM
Wong
Pancras C
PC
He
Kan
K
Morin
Paul E
PE
Chang
Chong-Hwan
CH
Cheney
Daniel L
DL
Knabb
Robert M
RM
Wexler
Ruth R
RR
Lam
Patrick Y S
PY
D000284:Administration, Oral; D000818:Animals; D000990:Antithrombin III / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001166:Arteriovenous Shunt, Surgical; D001665:Binding Sites; D001682:Biological Availability; D023421:Models, Animal; D010880:Piperidines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology; D062367:ortho-Aminobenzoates / Q000737:chemistry*
D010880:Piperidines; D011728:Pyridones; D015842:Serine Proteinase Inhibitors; D062367:ortho-Aminobenzoates; D000990:Antithrombin III; C000219:anthranilamide