(Z)-1-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-5-yl]-3-phenyl-urea | 1236290-87-1

• 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)-1-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-5-yl]-3-phenyl-urea
• 英文别名: (Z)-1-(3-((1H-Pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-3-phenylurea；1-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-5-yl]-3-phenylurea
• CAS: 1236290-87-1
• 化学式: C₂₀H₁₆N₄O₂
• 分子量: 344.373
• InChiKey: OTQANIANIYQLPE-BOPFTXTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-吡咯甲醛 、 1-(2-oxo-2,3-dihydro-1H-indol-5-yl)-3-phenylurea 在 四氢吡咯 作用下， 以 乙醇 为溶剂， 以70%的产率得到(Z)-1-[2-oxo-3-(1H-pyrrol-2-ylmethylene)-2,3-dihydro-1H-indol-5-yl]-3-phenyl-urea
  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.