bms-740808 and apixaban

bms-740808 has been researched along with apixaban* in 1 studies

Other Studies

1 other study(ies) available for bms-740808 and apixaban

ArticleYear
Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation fa
    Journal of medicinal chemistry, 2007, Nov-01, Volume: 50, Issue:22

    Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P1 moieties that resulted in the identification of the p-methoxyphenyl P1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

    Topics: Administration, Oral; Animals; Biological Availability; Blood Coagulation; Crystallography, X-Ray; Dogs; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; In Vitro Techniques; Models, Molecular; Molecular Structure; Pyrazoles; Pyridones; Rabbits; Structure-Activity Relationship

2007