Betrixaban

Cas No.:	330942-05-7
Chemical Name:	Betrixaban
Synonyms:	Betrixaban;N-(5-chloropyridin-2-yl)-2-({[4-(N,N-dimethylcarbamimidoyl)phenyl]carbonyl}amino)-5-methoxybenzamide;PRT-054021;ABP000384;Betrixaban (USAN);CHEBI:559679;CHEMBL512351;DNC009421;N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide;PRT 054021;QCR-99;SureCN158591;UNII-74RWP7W0J9;N-(5-Chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide
SMILES:	N=C(N(C)C)C(C=C1)=CC=C1C(NC2=CC=C(OC)C=C2C(NC(C=C3)=NC=C3Cl)=O)=O
Formula:	C23H22N5O3Cl
M.Wt:	451.90548
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Betrixaban is a highly potent, selective, and orally efficacious factor Xa (fXa) inhibitor with IC50 of 1.5 nM.
In Vivo:	Dosed at 0.5 mg/kg IV and 2.5 mg/kg PO, Betrixaban has bioavailability of 51.6% in dog; dosed at 0.75 mg/kg IV and 7.5 mg/kg PO, Betrixaban has bioavailability of 58.7% in monkey[1]. Both Betrixaban and Apixa-ban-mediated whole-blood INR increases are similarly reversed by r-Antidote. After i.v. infusion of the three fXa inhibitors (each admin¬istered individually) for 30 min, the total plasma concentrations of rivaroxaban, Betrixaban and apixaban are 1.4±0.4 μM (mean±s.d.), 0.2±0.01 μM and 1.4±0.3 μM, respectively, and the percentages of unbound inhibitor are 2.2%±0.8% (mean±s.d.), 40%±7.2% and 1.5%±0.3%, respectively. After administration of r-Antidote, the total plasma concentrations of the inhibitors increased to 1.9±0.09 μM, 2.0±0.4 μM and 4.2±0.7 μM, respectively, and the percentage of unbound inhibitor declined to 0%, 0.3%±0.1% and 0.05%±0.02%, respectively. Thus, for each of the three inhibitors, correction of prothrombin time by r-Antidote to near-normal values is associated with a reduction in the free fraction of the inhibitor[2].
In Vitro:	In patch clamp hERG assays, Betrixaban has IC50 of 8.9 μM. The plasma kallikrein IC50 and Ki values for Betrixaban are 6.3 μM and 3.5 μM respectively. Betrixaban (hERG Ki 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG Ki⩽0.5 μM)[1].