2-{4-[(S)-1-((S)-2-tert-Butoxycarbonyl-1-{1-[(S)-2-carbamoyl-1-((S)-2-naphthalen-1-ylmethyl-pent-4-enylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-ethyl)-allyl]-phenyl}-malonic acid di-tert-butyl ester | 641638-42-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-{4-[(S)-1-((S)-2-tert-Butoxycarbonyl-1-{1-[(S)-2-carbamoyl-1-((S)-2-naphthalen-1-ylmethyl-pent-4-enylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-ethyl)-allyl]-phenyl}-malonic acid di-tert-butyl ester
• CAS: 641638-42-8
• 化学式: C₅₅H₇₄N₄O₁₀
• 分子量: 951.213
• InChiKey: HRWBAZVEKYEVDZ-OLVSANEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.95
• 重原子数：
  69.0
• 可旋转键数：
  21.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  209.29
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2-{4-[(S)-1-((S)-2-tert-Butoxycarbonyl-1-{1-[(S)-2-carbamoyl-1-((S)-2-naphthalen-1-ylmethyl-pent-4-enylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-ethyl)-allyl]-phenyl}-malonic acid di-tert-butyl ester 在 三乙基硅烷 、 [((PCy₃)(Im(2,4,6-trimethylphenyl)2)Ru=CHPh)] 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 41.0h， 生成 2-{4-[(9S,10S,14S,18S)-7,16,19-triaza-18-(carbamoylmethyl)-9-carboxymethyl-14-(naphthylmethyl)-8,17,20-trioxospiro[5,14]icos-11-en-10-yl]phenyl}propanedioic acid
  参考文献：
  名称：

  Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

  摘要：

  Macrocyclization from the phosphotyrosyl. (pTyr) mimetic's beta-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

  DOI：

  10.1021/jm030510e
• 作为产物：
  描述：

  2-{4-[(1E)-3-((4S)-2-oxo-4-phenyl-(1,3-oxazolidin-3-yl))-3-oxoprop-1-enyl]phenyl}propane-1,3-dioic acid bis(1,1-dimethylethyl) ester 在 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 双氧水 、 sodium hexamethyldisilazane 、 苯硫酚铜(I) 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.33h， 生成 2-{4-[(S)-1-((S)-2-tert-Butoxycarbonyl-1-{1-[(S)-2-carbamoyl-1-((S)-2-naphthalen-1-ylmethyl-pent-4-enylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-ethyl)-allyl]-phenyl}-malonic acid di-tert-butyl ester
  参考文献：
  名称：

  Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands

  摘要：

  Macrocyclization from the phosphotyrosyl. (pTyr) mimetic's beta-position has previously been shown to enhance Grb2 SH2 domain-binding affinity of phosphonate-based analogues. The current study examined the effects of such macrocyclization using a dicarboxymethyl-based pTyr mimetic. In extracellular assays affinity was enhanced approximately 5-fold relative to an open-chain congener. Enhancement was also observed in whole-cell assays examining blockade of Grb2 binding to the erbB-2 protein-tyrosine kinase.

  DOI：

  10.1021/jm030510e