(E)-1-(4-(2-fluoroethoxy)benzyl)-3-((E)-3-(4-nitrophenyl)allylidene)indolin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-1-(4-(2-fluoroethoxy)benzyl)-3-((E)-3-(4-nitrophenyl)allylidene)indolin-2-one
• 英文别名: (3E)-1-{[4-(2-fluoroethoxy)phenyl]methyl}-3-[(2E)-3-(4-nitrophenyl)prop-2-en-1-ylidene]-2,3-dihydro-1H-indol-2-one；(3E)-1-[[4-(2-fluoroethoxy)phenyl]methyl]-3-[(E)-3-(4-nitrophenyl)prop-2-enylidene]indol-2-one
• 化学式: C₂₆H₂₁FN₂O₄
• 分子量: 444.462
• InChiKey: AOIUAVCQCDCNFO-NBWHZJRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(bromomethyl)-4-(2-fluoroethoxy)benzene 、 (Z)-3-((E)-3-(4-nitrophenyl)allylidene)indolin-2-one 、 (E)-3-((E)-3-(4-nitrophenyl)allylidene)indolin-2-one 在 sodium hydride 作用下， 反应 8.25h， 以61%的产率得到(Z)-1-(4-(2-fluoroethoxy)benzyl)-3-((E)-3-(4-nitrophenyl)allylidene)indolin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils

  摘要：

  A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (alpha-syn), beta amyloid (A beta), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity for alpha-syn and no selectivity for alpha-syn versus A beta or tau fibrils. Homologation to the corresponding diene analogues yielded a mixture of Z,E and E,E isomers; substitution of the indoline nitrogen with an N-benzyl group resulted in increased binding to alpha-syn and reasonable selectivity for alpha-syn versus and tau. Introduction of a para-nitro group into the benzene ring of the diene enabled separation of the Z,E and E,E isomers and led to the identification of the Z,E configuration as the more active regioisomer. The data described here provide key structural information in the design of probes which bind preferentially to alpha-syn versus A beta or tau fibrils.

  DOI：

  10.1021/acs.jmedchem.5b00571

文献信息

• Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils
  作者：Wenhua Chu、Dong Zhou、Vrinda Gaba、Jialu Liu、Shihong Li、Xin Peng、Jinbin Xu、Dhruva Dhavale、Devika P. Bagchi、André d’Avignon、Naomi B. Shakerdge、Brian J. Bacskai、Zhude Tu、Paul T. Kotzbauer、Robert H. Mach

  DOI：10.1021/acs.jmedchem.5b00571

  日期：2015.8.13

  A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (alpha-syn), beta amyloid (A beta), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity for alpha-syn and no selectivity for alpha-syn versus A beta or tau fibrils. Homologation to the corresponding diene analogues yielded a mixture of Z,E and E,E isomers; substitution of the indoline nitrogen with an N-benzyl group resulted in increased binding to alpha-syn and reasonable selectivity for alpha-syn versus and tau. Introduction of a para-nitro group into the benzene ring of the diene enabled separation of the Z,E and E,E isomers and led to the identification of the Z,E configuration as the more active regioisomer. The data described here provide key structural information in the design of probes which bind preferentially to alpha-syn versus A beta or tau fibrils.