Purity: > 98%
|IUPAC Name:||methyl (2R,3R)-2-[(3-carbamimidoylphenyl)methyl]-3-[[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]amino]butanoate|
Otamixaban(cas 193153-04-7) is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa. In vivo experiments have demonstrated that Otamixaban is highly efficacious in rodent, canine and porcine models of thrombosis. In addition, recent clinical findings indicate that Otamixaban is efficacious, safe and well tolerated in humans and therefore has considerable potential for the treatment of acute coronary syndrome. This review article chronicles the discovery and pre-clinical data surrounding the fXa inhibitor Otamixaban as well as the recent clinical findings in humans.
1. J Pharm Anal. 2014 Jun;4(3):197-204. doi: 10.1016/j.jpha.2013.10.001. Epub 2013
Enantiomeric characterization and structure elucidation of Otamixaban.
Shen J(1), Yang J(1), Heyse W(2), Schweitzer H(2), Nagel N(2), Andert D(2), Zhu
C(1), Morrison V(1), Nemeth GA(1), Chen TM(1), Zhao Z(1), Ayers TA(1), Choi
(1)Sanofi, 1041 Route 202-206, Bridgewater, NJ 08807, United States.
(2)Sanofi, Industriepark Hoechst Bldg., D-65926 Frankfurt, Germany.
Otamixaban is a potent (Ki=0.5 nM) fXa inhibitor currently in late-stage clinical
development at Sanofi for the management of acute coronary syndrome. Being
unproductive in obtaining a suitable crystal of Otamixaban, the required
enantiomeric characterization has been accomplished using vibrational circular
dichroism (VCD) spectroscopy. Selected by a spectrum similarity index, the
calculated spectra of several higher energy conformers were found to match well
with the observed spectra. The characteristic IR bands of these conformers were
also identified and attributed to the solvation effect. Combined with both the
single crystal x-ray diffraction results for an intermediate and the proton NMR
study, the absolute configuration of Otamixaban is unambiguously determined to be
2. Lancet. 2009 Sep 5;374(9692):762-4. doi: 10.1016/S0140-6736(09)61529-4. Epub 2009
Otamixaban in acute coronary syndromes.
Eikelboom JW(1), Weitz JI.
(1)Thrombosis Service, Hamilton General Hospital, Hamilton, ON, Canada L8L 2X2.
3. Clin Pharmacol Ther. 2006 Dec;80(6):691-702.
Direct and rapid inhibition of factor Xa by otamixaban: a pharmacokinetic and
pharmacodynamic investigation in patients with coronary artery disease.
Hinder M(1), Frick A, Jordaan P, Hesse G, Gebauer A, Maas J, Paccaly A.
(1)Science & Medical Affairs, Sanofi-Aventis, Frankfurt am Main, Germany.
BACKGROUND: New anticoagulants that combine effective anticoagulation with low
bleeding rates are still sought after. We investigated the safety,
pharmacokinetics, and pharmacodynamics of otamixaban, a direct factor Xa
inhibitor, in patients with stable coronary artery disease.
METHODS: This was a randomized, placebo-controlled, double-blind, multicenter
study in 119 patients with stable coronary artery disease taking maintenance
doses of their comedication. Of these patients, 50% had mild renal impairment
(creatinine clearance >45 mL/min but <80 mL/min). Patients were randomized in a
4:1 ratio to receive either otamixaban or placebo as a 1-minute bolus followed by
a 24-hour continuous infusion. Anti-factor Xa activity, clotting times (activated
partial thromboplastin time, dilute prothrombin time, Russell's viper venom
test), and international normalized ratio were measured.
RESULTS: All patients completed the study according to the protocol. No major or
minor bleeding occurred according to Thrombosis in Myocardial Infarction
criteria. Anti-factor Xa activity and anticoagulant effect were measurable early
after the start of the infusion and remained during the infusion. Upon cessation,
these effects declined rapidly and returned to baseline within 6 hours after the
end of infusion. Anti-factor Xa activity coincided with the otamixaban plasma
concentrations. The fold changes from baseline at the end of infusion with regard
to the clotting times ranged from 1.7 to 4.4 (1.15 for placebo), 1.29 to 3.15
(0.98 for placebo), and 1.19 to 2.11 (0.94 for placebo) for Russell's viper venom
test, dilute prothrombin time, and activated partial thromboplastin time,
respectively, and ranged from 0.94 to 1.70 (0.94 for placebo) for the
international normalized ratio.
CONCLUSION: In patients with stable coronary artery disease taking maintenance
doses of their usual concomitant medication, otamixaban exerts a rapid onset of
anticoagulation and anti-factor Xa activity. Our data provide evidence that
further studies are warranted to investigate the safety and efficacy of
otamixaban in the target population.