3-(2-(S)-azido-3-(4-((bis(tert-butyl)phosphono)methyl)phenyl)propanoyl)-4(S)-benzyl-1,3-oxazolidin-2-one | 300583-40-8

• 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: 3-(2-(S)-azido-3-(4-((bis(tert-butyl)phosphono)methyl)phenyl)propanoyl)-4(S)-benzyl-1,3-oxazolidin-2-one
• 英文别名: (4S)-3-[(2S)-2-azido-3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphorylmethyl]phenyl]propanoyl]-4-benzyl-1,3-oxazolidin-2-one
• CAS: 300583-40-8
• 化学式: C₂₈H₃₇N₄O₆P
• 分子量: 556.599
• InChiKey: TXJLQPNCAUGYOW-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(2-(S)-azido-3-(4-((bis(tert-butyl)phosphono)methyl)phenyl)propanoyl)-4(S)-benzyl-1,3-oxazolidin-2-one 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 3-(2(S)-azido-3-(4-(bis(tert-butyl)phosphono)methyl)phenyl)propanoic acid 、 3-(2(R)-azido-3-(4-(bis(tert-butyl)phosphono)methyl)phenyl)propanoic acid
  参考文献：
  名称：

  Heck反应在新的α-叠氮基磷酸酪氨酸模拟物的合成中的用途，该模拟物被适当地保护用于肽合成。

  摘要：

  DOI：

  10.1021/jo000643x
• 作为产物：
  描述：

  (S)-3-acryloyl-4-benzyloxazolidin-2-one 在 palladium diacetate 、 钯 2,4,5-triisopropyl benzenesulfonyl azide 、 氢气 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， -78.0~85.0 ℃ 、275.8 kPa 条件下， 生成 3-(2-(S)-azido-3-(4-((bis(tert-butyl)phosphono)methyl)phenyl)propanoyl)-4(S)-benzyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Heck反应在新的α-叠氮基磷酸酪氨酸模拟物的合成中的用途，该模拟物被适当地保护用于肽合成。

  摘要：

  DOI：

  10.1021/jo000643x

文献信息

• Sh2 domain binding inhibitors
  申请人：——

  公开号：US20040048788A1

  公开（公告）日：2004-03-11

  Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is 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 compounds of the present invention have the advantage that their conformation is constrained to provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical composition comprising a pharmaceutically or pharmacologically acceptable carrier and a compound of the present invention, a method for inhibiting an SH2 domain from binding with a phosphoprotein comprising contacting an SH2 domain with a compound of the present invention, a method of preventing or treating a disease, state, or condition by the use of one or more of these compounds, and a method for preparing the compounds of the present invention. The present invention further provides intermediates useful in the preparation of the compounds.

  本发明涉及用于SH2结构域结合抑制的化合物。例如，本发明揭示了一种式（I）的化合物，其中R1是脂肪族；R2与苯环结合，是苯基磷酸酯类似物基团或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被取代为从卤素、羟基、羧基、氨基、氨基烷基、烷基、烷氧基和酮中选择的取代基；R6是连接子；AA是氨基酸；n为1至6；或其盐。本发明的化合物具有优点，其构象被限制以提供与SH2结构域蛋白的增强结合亲和力。本发明还揭示了一种制备本发明化合物的中间体，以及包括药学或药理学可接受载体和本发明化合物的制药组合物、通过使用这些化合物中的一种或多种来预防或治疗疾病、状态或病况的方法，以及通过将SH2结构域与本发明化合物接触来抑制SH2结构域与磷酸化蛋白结合的方法。
• SH2 DOMAIN BINDING INHIBITORS
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP1383792A2

  公开（公告）日：2004-01-28
• US6977241B2
  申请人：——

  公开号：US6977241B2

  公开（公告）日：2005-12-20
• [EN] SH2 DOMAIN BINDING INHIBITORS<br/>[FR] INHIBITEURS DE LIAISON AU DOMAINE SH2
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2002016407A2

  公开（公告）日：2002-02-28

  Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is 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 compounds of the present invention have the advantage that their conformation is constrained to provide enhanced binding affinity with SH2 domain protein. Also disclosed are a pharmaceutical composition comprising a pharmaceutically or pharmacologically acceptable carrier and a compound of the present invention, a method for inhibiting an SH2 domain from binding with a phosphoprotein comprising contacting an SH2 domain with a compound of the present invention, a method of preventing or treating a disease, state, or condition by the use of one or more of these compounds, and a method for preparing the compounds of the present invention. The present invention further provides intermediates useful in the preparation of the compounds.
• Use of a Heck Reaction for the Synthesis of a New α-Azido Phosphotyrosyl Mimetic Suitably Protected for Peptide Synthesis
  作者：Terrence R. Burke、Ding-Guo Liu、Yang Gao

  DOI：10.1021/jo000643x

  日期：2000.9.1