| CAS |
No.330942-05-7 |
| 中文名称 |
贝曲西班 |
| 英文名称 |
Betrixaban |
| 别名 |
PRT054021 |
| 分子式 |
C23H22ClN5O3 |
| 分子量 |
451.91 |
| 溶解性 |
Soluble in DMSO(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD16038040 |
| SMILES |
CN(C)C(=N)C1=CC=C(C=C1)C(=O)NC2=C(C=C(C=C2)OC)C(=O)NC3=NC=C(C=C3)Cl |
| InChIKey |
XHOLNRLADUSQLD-UHFFFAOYSA-N |
| InChI |
InChI=1S/C23H22ClN5O3/c1-29(2)21(25)14-4-6-15(7-5-14)22(30)27-19-10-9-17(32-3)12-18(19)23(31)28-20-11-8-16(24)13-26-20/h4-13，25H，1-3H3，(H，27，30)(H，26，28，31) |
| PubChem CID |
10275777 |
| 靶点 |
Factor Xa |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
Betrixaban是一种有效的，选择性 factor Xa 抑制剂。 |
| 生物活性 |
Betrixaban (PRT054021) is a highly potent， selective， and orally efficacious factor Xa (fXa) inhibitor with an IC50 of 1.5 nM. Betrixaban shows antithrombotic effect.[1-3] |
| IC50 |
IC50: 1.5 nM (fXa)[1]Ki: 0.117 nM (fXa)， 1.8 μM (hERG)[1] |
| In Vitro |
Betrixaban (PRT054021) shows IC50 of 8.9 μM in patch clamp hERG assays[1]. Betrixaban shows an IC50 and a Ki of 6.3 μM and 3.5 μM for the plasma kallikrein， respectively[1]. Betrixaban (hERG Ki 1.8 μM) exhibits significantly lower hERG activity than all the others (hERG Ki?0.5 μM)[1].Betrixaban (5-25 ng/mL) inhibits thrombin generation[3]. |
| In Vivo |
Betrixaban (0.5 mg/kg， i.v.; 2.5 mg/kg， p.o.) has oral bioavailability of 51.6% in dog[1]. Betrixaban (0.75 mg/kg， i.v.; 7.5 mg/kg， p.o.) has oral bioavailability of 58.7% in monkey[1]. Betrixaban mediated whole-blood INR increase is reversed by r-Antidote. After i.v. infusion for 30 min， the total plasma concentrations of Betrixaban is 0.2±0.01 μM， and the percentages of unbound inhibitor is 40%±7.2%. After administration of r-Antidote， the total plasma concentration increased to 2.0±0.4 μM， and the percentage of unbound inhibitor declined to 0.3%±0.1%[2].Betrixaban (3 mg/kg) shows nearly comparable inhibition of thrombus mass to enoxaparin 1.6 mg/kg (76% vs 96% inhibition) in the rabbit abdominal vena cava model of clot accretion on cotton threads[3].Betrixaban (19.1 mg/kg) is at least as effective at maintaining patency as enoxaparin 7.6 mg/kg and clopidogrel 3 mg/kg/d (90% vs 70% vs 80% patency， respectively) in the ferric chloride injury model of rodent carotid artery[3]. |
| 动物实验 |
Rats[2] Whole-blood INR values (mean±s.d.) in rats infused with Betrixaban (1 mg/kg per hour) or vehicle and then treated with either vehicle or r-Antidote by i.v. bolus (6 mg) over 5 min plus infusion (9 mg/h) for up to 90 min. Circles， vehicle+vehicle; squares， Betrixaban + vehicle; triangles， Betrixaban + r-Antidote. *P≤0.02 compared to the r-Antidote treatment group determined by unpaired two-tailed t test. Whole-blood INR values (mean±s.d.) in rats infused with Apixaban (0.5 mg per kg body weight h?1) or vehicle and then treated with either vehicle or r-Antidote by i.v. bolus (6 mg) over 5 min plus infusion (6 mg/h) for up to 90 min. Circles， vehicle + vehicle; squares， apixaban + vehicle; triangles， apixaban+r-Antidote. *P≤0.01 compared to the r-Antidote treatment group determined by unpaired two-tailed t test. |
| 数据来源文献 |
[1]. Zhang P， et al. Discovery of Betrixaban (PRT054021)， N-(5-chloropyridin-2-yl)-2-(4-(N，N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide， a highly potent， selective， and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):21
[2]. Lu G， et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013 Apr;19(4):446-51.
[3]. Chan NC， et al. Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51. |
| 规格 |
5mg 10mg 50mg 100mg |
| 单位 |
瓶 |
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英语
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