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228559-41-9(anhydrous) 分子结构
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1-(2,4-difluorophenyl)-3-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-2-fluorophenyl}urea

ChemBase编号:72637
分子式:C24H18F3N3O4
平均质量:469.4126296
单一同位素质量:469.12494073
SMILES和InChIs

SMILES:
c1cnc2c(c1Oc1ccc(c(c1)F)NC(=O)Nc1ccc(cc1F)F)cc(c(c2)OC)OC
Canonical SMILES:
COc1cc2nccc(c2cc1OC)Oc1ccc(c(c1)F)NC(=O)Nc1ccc(cc1F)F
InChI:
InChI=1S/C24H18F3N3O4/c1-32-22-11-15-20(12-23(22)33-2)28-8-7-21(15)34-14-4-6-19(17(27)10-14)30-24(31)29-18-5-3-13(25)9-16(18)26/h3-12H,1-2H3,(H2,29,30,31)
InChIKey:
LFKQSJNCVRGFCC-UHFFFAOYSA-N

引用这个纪录

CBID:72637 http://www.chembase.cn/molecule-72637.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
1-(2,4-difluorophenyl)-3-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-2-fluorophenyl}urea
IUPAC传统名
1-(2,4-difluorophenyl)-3-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-2-fluorophenyl}urea
别名
1-(2,4-Difluoro-phenyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-urea 水合物
Ki8751 水合物
1-(2,4-Difluoro-phenyl)-3-[4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-urea hydrate
Ki8751 hydrate
Ki8751
CAS号
228559-41-9(anhydrous)
228559-41-9
MDL号
MFCD09971092
PubChem SID
162037562
PubChem CID
11317348

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
PubChem 11317348 external link

理论计算性质

理论计算性质

JChem
Acid pKa 10.212159  质子受体
质子供体 LogD (pH = 5.5) 4.3976107 
LogD (pH = 7.4) 4.8761487  Log P 4.8893604 
摩尔折射率 119.7905 cm3 极化性 45.128998 Å3
极化表面积 81.71 Å2 可自由旋转的化学键
里宾斯基五规则 true 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
DMSO: >20 mg/mL expand 查看数据来源
外观
white solid expand 查看数据来源
保存条件
-20°C expand 查看数据来源
欧盟危险性物质标志
有害性(Harmful) 有害性(Harmful) (Xn) expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
危险公开号
22-38 expand 查看数据来源
安全公开号
37 expand 查看数据来源
GHS危险品标识
GHS07 expand 查看数据来源
GHS警示词
Warning expand 查看数据来源
GHS危险声明
H315 expand 查看数据来源
个人保护装置
dust mask type N95 (US), Eyeshields, Gloves expand 查看数据来源
保存温度
-20°C expand 查看数据来源
作用靶点
c-Kit expand 查看数据来源
FGFR expand 查看数据来源
PDGFR expand 查看数据来源
VEGFR expand 查看数据来源
纯度
≥98% (HPLC) expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
Empirical Formula (Hill Notation)
C24H18F3N3O4 · xH2O expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
Selleck Chemicals -  S1363 external link
Research Area
Description Cancer
Biological Activity
Description Ki8751 is a potent and selective inhibitor of VEGFR2 with IC50 of 0.9 nM.
Targets VEGFR2 PDGFRα c-Kit FGFR-2
IC50 0.9 nM 67 nM 40 nM 170 nM [1]
In Vitro Ki8751 potently and selectively inhibits VEGFR2 with IC50 of 0.9 nM. Ki8751 also inhibits PDGFRα, c-Kit, and FGFR-2, with much higher IC50 values (40 nM–170 nM). Except for these several kinases, Ki8751 doesn’t disturb other kinases, including HGFR, EGFR, and InsulinR, even at 10 μM. [1]In human umbilical vein endothelial cells (HUVECs), Ki8751 (1 nM–100 nM) effectively decreases VEGF-stimulated cell proliferation and vasculature permeability. [2]In metastatic colorectal cancer (CRC) cells MIP, RKO, SW620, and SW480, but not in HCT116, Ki8751 (10 nM) increases cellular senescence. [3]
In Vivo In nude mice bearing human tumor xenografts of GL07, St-4, LC6, DLD-1, and A375 cells, Ki8751 (20 mg/kg) inhibits tumor growth. In nude rat xenograft models of LC-6 cells, Ki8751 (5 mg/kg) completely inhibits tumor growth without affecting body weight. [1]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Cellular Kinase Assays NIH3T3 cells prepared by transfection of human KDR. The cells are cultured in a collagen type I coated 96-well plate in an amount of 1.5 × 104 per well. The medium is then replaced by a DMEM medium containing 0.1% FCS. Ki8751 diluted in DMSO is added to each well and cultured. rhVEGF is added to a final concentration of 100 ng/mL, and the stimulation of cells is carried out at 37 °C. The cells are washed with PBS (pH 7.4), 50 μL of a solubilization buffer (20 mM HEPES (pH 7.4), 150 mM NaCl, 0.2% Triton X-100, 10% glycerol, 5 mM Na3VO4, 5 mM disodium ethylenediamine tetraacetate, and 2 mM Na4P2O7) is then added and a cell extract is prepared. Separately, PBS (50 μL, pH 7.4) containing 5 μg/mL of antiphosphotyrosine antibody (PY20) is added to a microplate for ELISA. After washing of the plate, 300 μL of a blocking solution is added. The cell extract is transferred to the plate. An anti-VEGFR2 antibody and a peroxidase-labeled anti-rabbit Ig antibody are added. Next, a chromophoric substrate for peroxidase is added, and the absorbance at 450 nm is measured with microplate reader. The VEGFR2 phosphorylation activity for each well is determined by presuming the absorbance with the addition of VEGF and without the addition of the test sample to be 100% VEGFR2 phosphorylation activity and VEGF to be 0% VEGFR2 phosphorylation activity. The concentration of the inhibition (%) of VEGFR2 Phosphorylation is determined for each case, and IC50 value is calculated.
Cell Assay [1]
Cell Lines HUVECs
Concentrations 1 nM–100 nM
Incubation Time 1 hour
Methods To evaluate the inhibition of VEGF-Stimulated HUVEC proliferation by Ki8751, HUVECs are plated at a density of 4000 cells/200 μL/well in a type I collagen pre-coated 96-well plates. After 24 hours, the cells are incubated for 1 hour with Ki8751 and then stimulated with 20 ng/mL rhVEGF. The cultures are incubated at 37 °C for 72 hours, then pulsed with 1 μCi/well [3H]thymidine and re-incubated for 14 hours. Cells are assayed for the incorporation of tritium using a beta counter.
Animal Study [1]
Animal Models Nude mice bearing human tumor xenografts of GL07, St-4, LC6, DLD-1, and A375 cells
Formulation
Doses 20 mg/kg
Administration Administered orally once a day for 9 consecutive days
References
[1] Kubo K, et al. J Med Chem, 2005, 48(5), 1359-1366.
[2] Tamura D, et al. Cancer Sci, 2010, 101(6), 1403-1408.
[3] Hasan MR, et al. Int J Cancer, 2011, 129(9), 2115–2123.
Sigma Aldrich -  K1265 external link
Biochem/physiol Actions
Ki8751 is a potent, selective inhibitor of VEGFR-2 tyrosine kinase (IC50 = 0.9 nM).

参考文献

参考文献

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