4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide

• ChemBase编号: 72561
• 分子式: C21H15ClF4N4O3
• 平均质量: 482.8154128
• 单一同位素质量: 482.07688092
• SMILES: c1nc(cc(c1)Oc1cc(c(cc1)NC(=O)Nc1ccc(c(c1)C(F)(F)F)Cl)F)C(=O)NC
• Canonical SMILES: CNC(=O)c1nccc(c1)Oc1ccc(c(c1)F)NC(=O)Nc1ccc(c(c1)C(F)(F)F)Cl
• InChI: InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
• InChIKey: FNHKPVJBJVTLMP-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
• IUPAC传统名: regorafenib
• 别名: 4-[4-[[[[4-Chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]-3-fluorophenoxy]-N-methyl-2-pyridinecarboxamide; 4-[4-[N’-(4-Chloro-3-trifluoromethylphenyl)ureido]-3-fluorophenoxy]pyridine-2-carboxylic Acid Methylamide; Regorafenib; Regorafenib; BAY 73-4506(Regorafenib); 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide

登记号

• CAS号: 755037-03-7
• MDL号: MFCD16038047
• PubChem SID: 162037486
• PubChem CID: 11167602

理论计算性质

• Acid pKa: 10.517571
• 质子受体: 3
• 质子供体: 3
• LogD (pH = 5.5): 4.485888
• LogD (pH = 7.4): 4.4857154
• Log P: 4.4860315
• 摩尔折射率: 114.7347 cm^3
• 极化性: 41.111164 Å^3
• 极化表面积: 92.35 Å^2
• 可自由旋转的化学键: 6
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: B-Raf; c-Kit; VEGFR

产品相关信息

• 纯度: 95+%
• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1178

Research Area

• Description: Cancer

Protocol

• Protocol: Kinase Assay ^[1]
• Kinase assays: In vitro assays using recombinant VEGFR2 (murine aa785–aa1367), VEGFR3 (murine aa818–aa1363), PDGFRβ (aa561–aa1106), Raf-1 (aa305–aa648) and BRafV600E (aa409–aa765) kinase domains are performed. Initial in vitro kinase inhibition profiling is performed at a fixed 1 μM Regorafenib concentration. Inhibitory concentration of 50% (IC50) values are determined from selected responding kinases, e.g., VEGFR1 and RET. TIE2 kinase inhibition is measured with a homogeneous time-resolved fluorescence (HTRF) assay using a recombinant fusion protein of glutathione-S-transferase, the intracellular domain of TIE2 and the peptide biotin-Ahx-EPKDDAYPLYSDFG as substrate.
• Protocol: Cell Assay ^[1]
• Cell Lines: GIST 882 and TT cells
• Concentrations: 5 nM-10 μM
• Incubation Time: 96 hours
• Methods: For proliferation assays, GIST 882 and TT cells are grown in RPMI medium containing L-glutamine, and MDA-MB-231, HepG2 and A375 cells in DMEM always containing 10% hiFBS. Cells are trypsinized, plated at 5×104 cells/well in 96-well plates in complete media containing 10% FBS and grown overnight at 37 °C. The next day, vehicle or Regorafenib serially diluted in complete growth media to between 10 μM and 5 nM final concentrations, and 0.2% DMSO, is added and incubation is continued for 96 hours. Cell proliferation is quantified.
• Protocol: Animal Study ^[1]
• Animal Models: Female athymic NCr nu/nu mice with Colo-205, MDA-MB-231 or 786-O
• Formulation: PEG400/125 mM aqueous methanesulfonic acid (80/20) or polypropylene glycol/PEG400/Pluronic F68 (42.5/42.5/15 + 20% Aqua)
• Doses: 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
• Administration: Orally

References

• References: [1] Wilhelm SM, et al. Int J Cancer, 2011, 129(1), 245-255.
• References: [2] Heng DY, et al. Ther Adv Med Oncol, 2010, 2(1), 39-49.
• References: [3] Carr BI, et al. J Cell Physiol, 2013, 228(2), 292-297.

Toronto Research Chemicals - R143000

It inhibits PDGFR tyrosine kinase with IC50=83nM. It is useful for the treatment of inflammation and as an anti-proliferative agent.

参考文献

• Wilhelm SM, et al. Int J Cancer, 2011, 129(1), 245-255.
• Heng DY, et al. Ther Adv Med Oncol, 2010, 2(1), 39-49.
• Carr BI, et al. J Cell Physiol, 2013, 228(2), 292-297.
• Leuner, C., et al.: Eur. J. Pharm. Biopharm., 50, 47 (2000)