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Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies
TLDR
In vivo, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits and potent and selective, with a Ki of 0.08 nm for human FXa.
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,
TLDR
Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.
Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.
TLDR
Highly selective, preorganized inhibitors with relatively low molecular weight and high oral bioavailability were synthesized and success in both displacing and mimicking the structural water molecule was confirmed by x-ray crystallographic studies.
Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable
TLDR
The optimization of the heterocyclic core, which ultimately led to the discovery of a novel pyrazole SN429, a highly potent, selective, and orally active factor Xa inhibitor which was chosen for clinical development is reported on.
Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.
  • P. Lam, Y. Ru, C. Hodge
  • Chemistry, Biology
    Journal of medicinal chemistry
  • 30 August 1996
TLDR
A novel class of cyclic ureas is designed and synthesized that incorporates a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking the transition-state mimic of the inhibitors.
Preclinical Pharmacokinetic and Metabolism of Apixaban, a Potent and Selective Factor Xa Inhibitor.
TLDR
The preclinical pharmacokinetic and metabolism attributes of apixaban feature a small volume of distribution, a low systemic clearance, good oral bioavailability, multiple elimination pathways and minimal potential for drug-drug interactions.
Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor
TLDR
Anti-fXa activity, prothrombin time (PT), and HEPTEST® clotting time (HCT) prolongation correlated well with plasma apixaban concentration in rat, dog and chimpanzee, suggesting a rapid onset of action of Apixaban.
In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor
TLDR
XM323 represents a novel class of potent inhibitors of human immunodeficiency virus (HIV) protease, and was shown to be equally effective against zidovudine-susceptible and zidovsky-resistant isolates of HIV-1, with an overall IC90 of 0.16 +/- 0.06 microM.
Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212).
TLDR
The discovery of a potent FXIa clinical candidate is described, 55 (FXIa Ki = 0.7 nM), with excellent preclinical efficacy in thrombosis models and aqueous solubility suitable for intravenous administration, which is focused on discovering an acute antithrombotic agent for use in a hospital setting.
Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies.
TLDR
Comparison of the high-resolution X-ray structures of the native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible, and cyclic cyanoguanidines were found to be very potent inhibitors of HIV- 1 protease.
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