bis(1,1-dimethylethyl) [[4-[3-oxo-3-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]propyl]phenyl]methyl]phosphonate | 491831-46-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: bis(1,1-dimethylethyl) [[4-[3-oxo-3-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]propyl]phenyl]methyl]phosphonate
• 英文别名: (4S)-3-[3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphorylmethyl]phenyl]propanoyl]-4-phenyl-1,3-oxazolidin-2-one
• CAS: 491831-46-0
• 化学式: C₂₇H₃₆NO₆P
• 分子量: 501.56
• InChiKey: RFRCEEAIAGXOBT-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  bis(1,1-dimethylethyl) [[4-[3-oxo-3-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]propyl]phenyl]methyl]phosphonate 在 lithium hydroxide 、 双氧水 、 sodium hexamethyldisilazane 、 N-氟苯磺酰胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (2S)-2-fluoro-4-[[bis(1,1-dimethoxyethoxy)phosphinyl]methyl]benzenepropanoic acid
  参考文献：
  名称：

  第一个α-氟-磷酸酪氨酰模拟物的合成

  摘要：

  摘要 (2S)-2-氟-4-[[双(1,1-二甲基乙氧基)膦基]甲基]苯丙酸 (5) 的非对映选择性制备是作为新的磷酸酪氨酰 (pTyr) 模拟物被适当保护以掺入肽中的。5 在手性诱导下合成 5，由市售的 Evans 助剂 (S)-(+)-4-苯基-2-恶唑烷酮提供。为了证明其合成效用，使用类似物 5 来制备信号转导导向的三肽。该肽的设计考虑及其初步生物学评估也包括在内。

  DOI：

  10.1081/scc-200034770
• 作为产物：
  描述：

  3-[(2E)-3-(4-{[bis(tert-butoxy)phosphono]methyl}phenyl)prop-2-enoyl]-(4S)-4-phenyl-1,3-oxazolidin-2-one 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以100%的产率得到bis(1,1-dimethylethyl) [[4-[3-oxo-3-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]propyl]phenyl]methyl]phosphonate
  参考文献：
  名称：

  Development of a Phosphatase-Stable Phosphotyrosyl Mimetic Suitably Protected for the Synthesis of High-Affinity Grb2 SH2 Domain-Binding Ligands

  摘要：

  Synthesis of (2R)-2-carboxymethyl-3-(4-(phosphonomethyl)phenyl) proprionic acid (5) in tert-butyl-protected form (6) and its use for the preparation of a Grb2 SH2 domain-directed tripeptide (8a) is reported. In extracellular ELISA-based assays, 8a exhibits potent Grb2 SH2 domain binding affinity (IC50=8 nM). Against cultures of MDA-MB-453 breast cancer cells, which overexpress erbB-2 tyrosine kinase, 8a is also antimitogenic at concentrations equivalent to those required to inhibit intracellular association of Grb2 protein with phosphorylated p185(erbB-2) protein (IC50=8 muM). Analogue 6 may be useful for the preparation of a variety of phosphatase-stable SH2 domain-directed ligands. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00527-9

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.
• Development of a Phosphatase-Stable Phosphotyrosyl Mimetic Suitably Protected for the Synthesis of High-Affinity Grb2 SH2 Domain-Binding Ligands
  作者：Chang-Qing Wei、Bihua Li、Ribo Guo、Dajun Yang、Terrence R Burke, Jr

  DOI：10.1016/s0960-894x(02)00527-9

  日期：2002.10

  Synthesis of (2R)-2-carboxymethyl-3-(4-(phosphonomethyl)phenyl) proprionic acid (5) in tert-butyl-protected form (6) and its use for the preparation of a Grb2 SH2 domain-directed tripeptide (8a) is reported. In extracellular ELISA-based assays, 8a exhibits potent Grb2 SH2 domain binding affinity (IC50=8 nM). Against cultures of MDA-MB-453 breast cancer cells, which overexpress erbB-2 tyrosine kinase, 8a is also antimitogenic at concentrations equivalent to those required to inhibit intracellular association of Grb2 protein with phosphorylated p185(erbB-2) protein (IC50=8 muM). Analogue 6 may be useful for the preparation of a variety of phosphatase-stable SH2 domain-directed ligands. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis of the First α‐Fluoro‐Phosphotyrosyl Mimetic
  作者：Zhen‐Dan Shi、Hongpeng Liu、Manchao Zhang、Dajun Yang、Terrence R. Burke

  DOI：10.1081/scc-200034770

  日期：2004.12.31

  Abstract The diastereoselective preparation of (2S)‐2‐fluoro‐4‐[[bis(1,1‐dimethylethoxy)phosphinyl]methyl] benzenepropanoic acid (5) is presented as new phosphotyrosyl (pTyr) mimetic suitably protected for incorporation into peptides. Synthesis of 5 utilized electrophilic fluorination under chiral induction provided by the commercially available Evans auxiliary, (S)‐(+)‐4‐phenyl‐2‐oxazolidinone. In

  摘要 (2S)-2-氟-4-[[双(1,1-二甲基乙氧基)膦基]甲基]苯丙酸 (5) 的非对映选择性制备是作为新的磷酸酪氨酰 (pTyr) 模拟物被适当保护以掺入肽中的。5 在手性诱导下合成 5，由市售的 Evans 助剂 (S)-(+)-4-苯基-2-恶唑烷酮提供。为了证明其合成效用，使用类似物 5 来制备信号转导导向的三肽。该肽的设计考虑及其初步生物学评估也包括在内。