BMS-740808

• 产品号: S1571
• CAS号: 280118-23-2
• 分子式: C31H27F3N6O3
• 分子量: 588.5796896
• 保 存: -20°C

产品别名

• 标题: BMS-740808
• IUPAC标准名: 1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one
• IUPAC传统名: 1-(3-amino-1,2-benzoxazol-5-yl)-6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-3-(trifluoromethyl)-4H,5H-pyrazolo[3,4-c]pyridin-7-one

产品登记号

• CAS号: 280118-23-2

产品性质

• 作用靶点: Factor Xa
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: BMS-740808 is a highly potent, selective inhibitor of blood coagulation factor Xa (fXa) with K_i with 0.03 nM.
• Targets: fXa; Rabbit AVshunt; Thrombin
• IC50: 0.03 nM (K_i); 135 nM; 35 nM (K_i) ^[1]
• In Vitro: BMS-740808 is highly potent with a rapid onset of inhibition (2.7 × 10^7 M^-1 s^-1), selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model. BMS-740808 is synthesized by modification of employing bicyclic pyrazolo-pyridinone scaffold to Razaxaban, a pyrazole based fXa inhibitor. Especially for BMS-740808, the introduction of a 3(R)-hydroxyl moiety on the pyrrolidine ring results in a significant enhancement in potency. BMS-740808 also shows the high affinity for thrombin. ^[1]
• In Vivo: The pharmacokinetic profile for BMS-740808 is comparable to that of Razaxaban with moderate half life, whereas BMS-740808 shows low clearance, low V_dss, moderate half life and high oral bio-availability, which is quite possibly due to the hydroxyl substituent on the cyclic amino moiety. ^[1]

Protocol

• Protocol: Kinase Assay ^[1]
• Ki Determination: FXa (1 nM) is added to a 96-well plate containing BMS-740808 (5 pM to 3 μM) in buffer A (20 mM HEPES, 0.15 M NaCl, 0.1% PEG-8000, 5 mM CaCl₂, pH 7.4). S-2765 (N-α-Z-d-Arg-Gly-Arg-p Nitroanilide) at 200 μM is added, and substrate hydrolysis is monitored at 405 nm. Data are analyzed by Batch K_i software.
• Protocol: Animal Study ^[1]
• Animal Models: Male rabbit AVShunt thrombosis model.
• Formulation: BMS-740808 is dissolved in saline.
• Doses: 2 μM
• Administration: Given as continuous i.v. infusion via the jugular vein

References

• References: [1] Pinto DJ, et al, Bioorg Med Chem Lett, 2006, 16(15), 4141-4147.

参考文献

• Pinto DJ, et al, Bioorg Med Chem Lett, 2006, 16(15), 4141-4147.