2-(4-溴苯基)-丙二酸-1,3-双叔丁酯 | 641638-37-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-溴苯基)-丙二酸-1,3-双叔丁酯
• 英文名称: 2-(4-bromophenyl)propane-1,3-dioic acid bis(1,1-dimethylethyl) ester
• 英文别名: Di-tert-butyl (4-bromophenyl)propanedioate；ditert-butyl 2-(4-bromophenyl)propanedioate
• CAS: 641638-37-1
• 化学式: C₁₇H₂₃BrO₄
• 分子量: 371.271
• InChiKey: DSFWQGCMVGWAON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-溴苯基)-丙二酸-1,3-双叔丁酯 在 palladium diacetate 、 苯硫酚铜(I) 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 19.33h， 生成 2-{4-[(1R)-3-((4S)-2-oxo-4-phenyl-(1,3-oxazolidin-3-yl))-3-oxo-1-vinylpropyl]phenyl}propane-1,3-dioic acid bis(1,1-dimethylethyl) 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
• 作为产物：
  描述：

  丙二酸二叔丁酯 、 对溴碘苯 在 六甲基磷酰三胺 、 sodium hydride 、 copper(I) bromide 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以75%的产率得到2-(4-溴苯基)-丙二酸-1,3-双叔丁酯
  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

文献信息

• Sh2 domain binding inhibitors
  申请人：Burke R. Terrence

  公开号：US20060167222A1

  公开（公告）日：2006-07-27

  Disclosed are compounds for SH2 domain binding inhibition, for example, a compound of formula (I), wherein R 1 is a lipophile; R 2 , in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R 3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R 3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R 6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The conformationally compounds provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical compositions and a method for inhibiting an SH2 domain from binding with a phosphoprotein.

  本发明揭示了用于SH2结构域结合抑制的化合物，例如，式(I)的化合物，其中R1是一个疏水基；R2与苯环结合，是苯基磷酸酯类似物基团或受保护的苯基磷酸酯类似物基团；R3是氢、叠氮基、氨基、羧基烷基、烷氧羰基烷基、氨基羰基烷基或烷基羰基氨基，其中R3的烷基部分可以选择地用来自卤素、羟基、羧基、氨基、氨基烷基、烷基、烷氧基和酮的取代基进行取代；R6是一个连接基；AA是一种氨基酸；n为1至6；或其盐。这些构象化合物提供了与SH2结构域蛋白的增强结合亲和力。本发明还揭示了一种制药组合物和一种抑制SH2结构域与磷酸化蛋白结合的方法。
• US7425537B2
  申请人：——

  公开号：US7425537B2

  公开（公告）日：2008-09-16
• [EN] SH2 DOMAIN BINDING INHIBITORS<br/>[FR] INHIBITEURS DE LIAISON AU DOMAINE SH2
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2004003005A2

  公开（公告）日：2004-01-08

  Disclosed are compounds for SH2 domain binding inhibition, for example, a compound of formula (I), wherein R1 is a lipophile; R2, in combination with the phenyl ring, is a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. The conformationally compounds provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical compositions and a method for inhibiting an SH2 domain from binding with a phosphoprotein.
• Macrocyclization in the Design of Non-Phosphorus-Containing Grb2 SH2 Domain-Binding Ligands
  作者：Zhen-Dan Shi、Chang-Qing Wei、Kyeong Lee、Hongpeng Liu、Manchao Zhang、Toshiyuki Araki、Lindsey R. Roberts、Karen M. Worthy、Robert J. Fisher、Benjamin G. Neel、James A. Kelley、Dajun Yang、Terrence R. Burke

  DOI：10.1021/jm030510e

  日期：2004.4.1

  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.