N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

• ChemBase编号: 72894
• 分子式: C23H15ClF2N4O3
• 平均质量: 468.8400064
• 单一同位素质量: 468.08007448
• SMILES: n1c(c(c(cc1)Oc1ccc(cc1F)NC(=O)c1c[nH]cc(c1=O)c1ccc(cc1)F)Cl)N
• Canonical SMILES: Fc1ccc(cc1)c1c[nH]cc(c1=O)C(=O)Nc1ccc(c(c1)F)Oc1ccnc(c1Cl)N
• InChI: InChI=1S/C23H15ClF2N4O3/c24-20-19(7-8-29-22(20)27)33-18-6-5-14(9-17(18)26)30-23(32)16-11-28-10-15(21(16)31)12-1-3-13(25)4-2-12/h1-11H,(H2,27,29)(H,28,31)(H,30,32)
• InChIKey: PDYXPCKITKHFOZ-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide
• IUPAC传统名: N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-5-(4-fluorophenyl)-4-oxo-1H-pyridine-3-carboxamide
• 别名: BMS794833; BMS 794833

登记号

• CAS号: 1174046-72-0
• PubChem SID: 162037814
• PubChem CID: 44155856

理论计算性质

• Acid pKa: 7.5738134
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 3.3428543
• LogD (pH = 7.4): 3.6726472
• Log P: 3.7644732
• 摩尔折射率: 120.7555 cm^3
• 极化性: 44.158302 Å^3
• 极化表面积: 106.34 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: c-Met; VEGFR

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S2201

Research Area

• Description: Cancer

Biological Activity

• Description: BMS794833 is a potent ATP competitive inhibitor of Met and VEGFR2 with IC50 of 1.7 nM and 15 nM, respectively.
• Targets: Met; VEGFR2
• IC50: 1.7 nM; 15 nM ^[1]
• In Vitro: BMS794833 also inhibits Met receptor activated gastric carcinoma cell line, GTL-16, with IC50 of 39 nM. ^[1]
• In Vivo: In GTL-16 human gastric tumor xenografts model, BMS798433 shows greater than 50% TGI for at least one tumor doubling time with no overt toxicity observed during 14 days. BMS798433 also shows complete tumor stasis at a dose of 25 mg/kg against U87 glioblastoma model. ^[1]
• Clinical Trials: BMS798433 is currently in Phase I clinical trial against advanced or metastatic solid tumor.

Protocol

• Protocol: Kinase Assay ^[1]
• Met kinase assay: BMS798433 is dissolved in DMSO and diluted by water before use. The reaction solution contains baculovirus expressed GST-Met kinase, 20 mM Tris-HCl (pH 7.4), 1 mM MnCl₂, 1 mM DTT, 0.1mg BSA, 0.1 mg polyGlu₄/tyr, 1μM ATP and 0.2μCi γ–ATP. Reactions are incubated at 30 °C for 1 hour and stopped by 8% TCA. TCA precipitates are collected onto GF/C plates using a universal harvester and the filters are quantitated using liquid scintillation counter.
• VEGFR2 assay: BMS798433 is dissolved in DMSO and diluted by water before use. The reaction solution contains 20 mM Tris-HCl (pH 7.4), 1 mM MnCl₂, 1 mM DTT, 0.1mg BSA, 75 μg polyGlu₄/tyr, 1μM ATP, 0.5 μCi γ–ATP and 7.5 ng/rxn enzyme stock (10% glycerol). The reaction is initiated by addition of enzyme and stopped by 30% TCA after 1 hour. Assays are prepared in 96 well plates and incubated at 27 °C for 1 hour. Then acid precipitated with TCA for 20 minutes on ice. Those precipitates are transferred to GF/C plates using a harvester and the filters are quantitated using liquid scintillation counter.
• Protocol: Cell Assay ^[1]
• Cell Lines: GTL-16 cells
• Concentrations: ~ 1 μM
• Incubation Time: 72 hours
• Methods: GTL-16 cells are seeded into 96 well plates and incubated for 24 hours. BMS798433 is dissolved in DMSO at 10 mM and diluted with culture medium before use. Then BMS798433 is added to the cells for 72 hours. After that, MTS assay is used to measure the IC50.
• Protocol: Animal Study ^[1]
• Animal Models: GTL-16 and U87 xenografts
• Doses: 25 mg/kg
• Administration: Orally once daily

References

• References: [1] WO2009094417A1

参考文献

• WO2009094417A1