(Z)-5-{6-[3-(4-chlorophenyl)-ureido]-2-oxo-1,2-dihydroindol-3-ylidene-methyl}-2,4-dimethyl-1H-pyrrole-3-carboxylic acid | 1236291-19-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-5-{6-[3-(4-chlorophenyl)-ureido]-2-oxo-1,2-dihydroindol-3-ylidene-methyl}-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
• 英文别名: 5-[(Z)-[6-[(4-chlorophenyl)carbamoylamino]-2-oxo-1H-indol-3-ylidene]methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
• CAS: 1236291-19-2
• 化学式: C₂₃H₁₉ClN₄O₄
• 分子量: 450.881
• InChiKey: RWCSLXSUPQHKBX-YVLHZVERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  123
• 氢给体数：
  5
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-3-(2-oxo-2,3-dihydro-1H-indol-6-yl)urea 、 2-(5-甲醛-2,4-二甲基-1H-吡咯-3-基)乙酸 在 四氢吡咯 作用下， 以 乙醇 为溶剂， 以60%的产率得到(Z)-5-{6-[3-(4-chlorophenyl)-ureido]-2-oxo-1,2-dihydroindol-3-ylidene-methyl}-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors

  摘要：

  A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.021

文献信息

• Synthesis and structure–activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors
  作者：Rahul R. Khanwelkar、Grace Shiahuy Chen、Hsiao-Chun Wang、Chao-Wu Yu、Chiung-Hua Huang、On Lee、Chih-Hung Chen、Chrong-Shiong Hwang、Ching-Huai Ko、Nien-Tzu Chou、Mai-Wei Lin、Ling-mei Wang、Yen-Chun Chen、Tzong-Hsiung Hseu、Chia-Ni Chang、Hui-Chun Hsu、Hui-Chi Lin、Ying-Chu Shih、Shuen-Hsiang Chou、Hsiang-Wen Tseng、Chih-Peng Liu、Chia-Mu Tu、Tsan-Lin Hu、Yuan-Jang Tsai、Ji-Wang Chern

  DOI：10.1016/j.bmc.2010.05.021

  日期：2010.7

  A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. (C) 2010 Elsevier Ltd. All rights reserved.