(4-bromomethylbenzyl)phosphonic acid di-tert-butyl ester | 166409-74-1

• 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: (4-bromomethylbenzyl)phosphonic acid di-tert-butyl ester
• 英文别名: 4-(di-tert-butylphosphonomethyl)-α-bromotoluene；4-(di-tert-butylphosphonomethyl)benzyl bromide；di(tert-butyl) [4-(bromomethyl)benzyl]phosphonate；di-tert-butyl (4-bromomethyl)benzyl phosphonate；1-[bis[(2-methylpropan-2-yl)oxy]phosphorylmethyl]-4-(bromomethyl)benzene
• CAS: 166409-74-1
• 化学式: C₁₆H₂₆BrO₃P
• 分子量: 377.258
• InChiKey: WHTRCUKEXDIONX-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C
• 沸点：
  426.6±33.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-bromomethylbenzyl)phosphonic acid di-tert-butyl ester 在 氢氧化钾 、 sodium hydroxide 、 二氧化碳 、 苄基三甲基氯化铵 、 碳酸氢钠 、 potassium carbonate 、 柠檬酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 Fmoc-(D,L)-(α-Me)Pmp(t-Bu2)-OH
  参考文献：
  名称：

  小磷酸肽，Grb2 SH2域抑制剂及其前药的构效关系。

  摘要：

  为开发针对癌症中HER2 / ErbB2过表达的潜在抗肿瘤药，我们设计了受体的磷酸酪氨酸与衔接蛋白Grb2的SH2结构域之间的识别抑制剂。在本文的第一部分中，我们报告了受约束的（α-Me）磷酸酪氨酸残基类似物的合成，例如（α-Me）-4-膦酰基甲基苯丙氨酸（-CH2PO3H2），（α-Me）4-膦酰基二氟甲基苯丙氨酸（- CF2PO3H2）和（α-Me）-4-膦酰基苯丙氨酸（-PO3H2）。这些残基在mAZ-pTyr-Xaa-Asn-NH2系列中的结合提供了对Grb2 SH2域具有非常高亲和力的化合物，其Kd值在10（-8）-10（-9）范围内。这些化合物可作为Grb2-Shc相互作用的有效拮抗剂。我们的结果强调了根据在mAZ-pTyr-（alphaMe）pTyr-Asn-NH2和Grb2 SH2域之间结晶的复合物中观察到的相互作用，由pY +1个氨基酸携带的双负电荷的重要性。mAZ-pT

  DOI：

  10.1021/jm031005k
• 作为产物：
  描述：

  二叔丁基亚磷酸盐 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 23.0h， 生成 (4-bromomethylbenzyl)phosphonic acid di-tert-butyl ester
  参考文献：
  名称：

  Concise and Enantioselective Synthesis of Fmoc-Pmp(Bu^t)₂-OH and Design of Potent Pmp-Containing Grb2-SH2 Domain Antagonists

  摘要：

  L-Phosphonomethylphenylalanine (L-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(Bu-t)(2)-OH was developed in order to incorporate the functionally significant L-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer.

  DOI：

  10.1021/ol035078+

文献信息

• Pseudopeptide compounds having an inhibiting activity with respect to paths activated by proteins with active tyrosine kinase activity and pharmaceutical compositions containing same
  申请人：——

  公开号：US20020055463A1

  公开（公告）日：2002-05-09

  The invention concerns a compound corresponding to general formula (1) wherein, in particular, R 2 represents a phenylmethyl or naphthylmethyl or cyclohexylmethyl radical, 2- and 3-pryidinylmethyl, substituted on the cycle in meta or para position by an acid group or an alkyl radical of the type (CH 2 ) n (with n=3 or 4) substituted in terminal position by an acid group; and R 3 represents a hydrogen group or a linear or branched C 1 -C 4 alkyl or alkylcycloalkyl with a C 3 -C 6 cycloalkyl. The invention also concerns the use of a compound of general formula (I) for preparing a pharmaceutical composition for treating diseases related to proliferative processes, cancers and/or metastases.

  该发明涉及与通式（1）相对应的化合物，其中特别是R2代表苯甲基、萘甲基或环己甲基基团，2-和3-吡啶基甲基，在环上以间位或对位被酸基或(CH2)n类型的烷基基团（其中n＝3或4）取代，末端位置被酸基取代；R3代表氢基团或线性或支链的C1-C4烷基或烷基环烷基，其中烷基环烷基为C3-C6环烷基。该发明还涉及利用通式（I）的化合物制备用于治疗与增殖过程、癌症和/或转移相关的疾病的药物组合物。
• New synthesis of D,L-fmoc protected 4- phosphonomethylphenylalanine derivatives and their enzymatic resolution
  作者：Krystyna baczko、Wang-Qing Liu、Bernard P. Roques、Christlane Garbay-Jaureguiberry

  DOI：10.1016/0040-4020(95)01003-3

  日期：1996.2

  enzymatic resolution of ethyl 4-[(dimethylphosphono)methyl]-D,L-phenylalaninate succeeded. These results are discussed by comparison with the literature data. The L and D amino acids were used to prepare separately, through solid-phase peptide synthesis, followed by deprotection of dimethylphosphonate group by trimethylsilyliodide (TMSI) in acetonitrile, the L and D isomers of Glu-Asp-Val- Pmp-Glu-Asn-Leu-His-Thr

  描述了适用于固相肽合成的N - Fmoc 4-膦酰基甲基-D，L-苯丙氨酸在二叔丁基或二甲基膦酸酯形式（Fmoc-Pmp（OR）2）保护下的新合成方法。这些O的水解稳定类似物的拆分通过非对映异构体盐的部分重结晶或使用枯草杆菌蛋白酶嘉士伯酯酶尝试了β-磷酸酪氨酸。只有4-[（（二甲基膦酰基）甲基]乙基-D，L-苯丙氨酸乙酯的酶促拆分成功。通过与文献数据进行比较来讨论这些结果。氨基酸的L和d被用来分别制备，通过固相肽合成，接着在乙腈中由三甲基甲dimethylphosphonate基的脱保护（TMSI），GLU-ASP-Val-的L和d异构体PMP -Glu-ASN -Leu-His-Thr，一种肽，对应于磷酸酶PTP 1C的潜在磷酸化位点。
• Phosphonic acids derivatives as inhibitors of protein tyrosine phosphate 1B (PTP-1B)
  申请人：Merck Frosst Canada & Co.

  公开号：US06174874B1

  公开（公告）日：2001-01-16

  The invention encompasses the novel class of compounds represented by formula I which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases.

  该发明涵盖了由公式I表示的新型化合物类，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了制药组合物和治疗或预防PTP-1B介导疾病的方法。
• Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines
  作者：Jennifer Dourlat、Wang-Qing Liu、Nohad Gresh、Christiane Garbay

  DOI：10.1016/j.bmcl.2007.02.016

  日期：2007.5

  Novel 1,4-benzodiazepine compounds were synthesized and evaluated for their ability to inhibit the proliferation of tumor cells. Some compounds revealed activities in the micromolar range and were more efficient than reference compound Ro 5-4864. Preliminary SAR helped to identify critical motifs for antiproliferative activity and led to the discovery of a compound selective for a melanoma cell line, known for its resistance to chemotherapy. (c) 2007 Elsevier Ltd. All rights reserved.
• Enantioselective synthesis of N-fmoc protected di-tert-butyl 4-phosphonomethyl-L-phenylalanine : a hydrolytically stable analogue of O-phosphotyrosine
  作者：Wang-Qing Liu、Bernard P. Roques、Christiane Garbay-Jaureguiberry

  DOI：10.1016/0957-4166(95)00050-y

  日期：1995.3

  Fmoc-L-Pmp(tBu)(2)-OH was prepared with high enantiomeric purity by an asymmetric synthetic pathway, using a camphor sultam as chiral auxiliary.