1-(溴甲基)-4-[二乙氧基磷酰基(二氟)甲基]苯 | 174678-80-9

• 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: 1-(溴甲基)-4-[二乙氧基磷酰基(二氟)甲基]苯
• 英文名称: diethyl [(4-α-bromomethyl)phenyldifluoromethyl]-phosphonate
• 英文别名: diethyl [(4-α-bromomethyl)phenyldifluoromethyl]phosphonate；4-{(diethoxyphosphoryl)(difluoro)methyl}benzyl bromide；[(4-bromomethyl-phenyl)difluoromethyl]-phosphonic acid diethyl ester；(4-bromomethylphenyl)difluoromethylphosphonic diethyl ester；[(4-Bromomethyl-phenyl)-difluoro-methyl]-phosphonic acid diethyl ester；1-(bromomethyl)-4-[diethoxyphosphoryl(difluoro)methyl]benzene
• CAS: 174678-80-9
• 化学式: C₁₂H₁₆BrF₂O₃P
• 分子量: 357.132
• InChiKey: FOVYBNXOSRNQOI-UHFFFAOYSA-N

物化性质

• 沸点：
  380.5±42.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(溴甲基)-4-[二乙氧基磷酰基(二氟)甲基]苯 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.5h， 生成 diethyl difluoro{4-[3-hydroxy-2-(hydroxymethyl)propyl]phenyl}methylphosphonate
  参考文献：
  名称：

  Enzymatic desymmetrization of prochiral 2-benzyl-1,3-propanediol derivatives: A practical chemoenzymatic synthesis of novel phosphorylated tyrosine analogues

  摘要：

  (Phosphonomethyl)phenylalanine (Pmp) and (phosphonodifluoromethyl)phenylalanine (F(2)Pmp) as well as their beta-amino acid congeners were prepared as a protecting variant amenable to the peptide synthesis from readily available 2-benzyl-1,3-propandiols possessing either a diethylphosphonomethyl- or diethylphosphonodifluoromethyl functionality at the para-position via the lipase-catalyzed desymmetrization. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00586-9
• 作为产物：
  描述：

  溴氟甲基膦酸二乙酯 在 N-溴代丁二酰亚胺(NBS) 、 镉 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 17.5h， 生成 1-(溴甲基)-4-[二乙氧基磷酰基(二氟)甲基]苯
  参考文献：
  名称：

  Structure of Protein Tyrosine Phosphatase 1B in Complex with Inhibitors Bearing Two Phosphotyrosine Mimetics

  摘要：

  Protein tyrosine phosphatases (PTPases) are signal-transducing enzymes that dephosphorylate intracellular proteins that have phosphorylated tyrosine residues. It has been demonstrated that protein tyrosine phosphatase 1B (PTP1B) is an attractive therapeutic target because of its involvement in regulating insulin sensitivity (Elcheby et al. Science 1999,283, 1544-1548). The identification of a second binding site in PTP1B (Puius et al., Proc. Natl. Acad. Sci. U.S.A 1997, 94, 13420-13425) suggests a new strategy for inhibitor design, where appropriate compounds may be made to simultaneously occupy both binding sites to gain much higher affinity and selectivity. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have determined the crystal structure of PTP1B complexed with two non-peptidyl inhibitors, 4 and 5, both of which contain two aryl difluoromethylenephosphonic acid groups, a nonhydrolyzable phosphate mimetic. The structures were determined and refined to 2.35 and 2.50 Angstrom resolution, respectively. Although one of the inhibitors seems to have satisfied the perceived requirement for dual binding, it did not bind both the active site and the adjacent noncatalytic binding site as expected. The second or distal phosphonate group instead extends into the solvent and makes water-mediated interactions with Arg-47. The selectivity of the more potent of these two inhibitors, as well as four other inhibitors bearing two such phosphate mimetics for PTP1B versus seven other PTPases, was examined, In general, selectivity was modest to good when compared to PTPases Cdc25a, PTPmeg-1, PTP beta, and CD45. However, selectivity was generally poor when compared to other PTPases such as SHP-1, SHP-2, and especially TCPTP, for which almost no selectivity was found. The implications these results have concerning the utility of dual-binding inhibitors are discussed.

  DOI：

  10.1021/jm010266w

文献信息

• Aryldifluoromethylphosphonic acids with sulfur-containing substituents as PTP-1B inhibitors
  申请人：——

  公开号：US20020002149A1

  公开（公告）日：2002-01-03

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

  本发明包括一类新颖的化合物，其通过以下公式表示，这些化合物是PTP-1B酶的抑制剂。 1 本发明还包括用于治疗或预防PTP-1B介导的疾病的药物组合物和方法，包括糖尿病。
• Structure−Activity Relationships of Small Phosphopeptides, Inhibitors of Grb2 SH2 Domain, and Their Prodrugs
  作者：Wang-Qing Liu、Michel Vidal、Catherine Olszowy、Emmanuelle Million、Christine Lenoir、Hélène Dhôtel、Christiane Garbay

  DOI：10.1021/jm031005k

  日期：2004.2.1

  affinity for the Grb2 SH2 domain, in the 10(-8)-10(-9) range of Kd values. These compounds behave as potent antagonists of the Grb2-Shc interaction. Our results highlight the importance of the doubly negative charge borne by the pY + 1 amino acid in accordance with the interactions observed in the complex crystallized between mAZ-pTyr-(alphaMe)pTyr-Asn-NH2 and the Grb2 SH2 domain. mAZ-pTyr-(alphaMe)pTyr-Asn-NH2

  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
• Synthesis of L-2,3,5,6-tetrafluoro-4-(phosphonomethyl) phenylalanine, a novel non-hydrolyzable phosphotyrosine mimetic and L-4-(phosphonodifluoromethyl)phenylalanine
  作者：Wang-Qing Liu、Bernard P. Roques、Christiane Garbay

  DOI：10.1016/s0040-4039(97)00027-0

  日期：1997.2

  A new non-hydrolyzable phosphotyrosine analogue, L-F4Pmp and its N-Fmoc protected derivative were prepared by using an enantioselective synthetic pathway with camphor sultam as chiral auxiliary. The side chain pKa2 (6.9) of L-F4Pmp was determined. A new synthesis of L-F2Pmp was also described.

  通过使用樟脑舒马坦作为手性助剂的对映选择性合成途径，制备了一种新的不可水解的磷酸酪氨酸类似物LF 4 Pmp及其受N-Fmoc保护的衍生物。测定了LF 4 Pmp的侧链pKa 2（6.9）。还描述了LF 2 Pmp的新合成。
• Phosphonic acid biaryl derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B)
  申请人：——

  公开号：US20020052346A1

  公开（公告）日：2002-05-02

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

  该发明涵盖了由公式I表示的新型化合物类别，这些化合物是PTP-1B酶的抑制剂。该发明还涵盖了制备药物组合物和治疗或预防PTP-1B介导的疾病的方法，包括糖尿病、肥胖症和与糖尿病相关的疾病。
• Trisubstituted nitrogen modulators of tyrosine phosphatases
  申请人：Semple E. Joseph

  公开号：US20060135773A1

  公开（公告）日：2006-06-22

  Compounds, compositions and methods are provided for modulating the activity of protein tyrosine phosphatases, including PTP-1B. In one embodiment, the compounds are N,N-dibenzylarylsulfonamides.

  提供了调节蛋白酪氨酸磷酸酶（包括PTP-1B）活性的化合物、组合物和方法。在一种实施例中，该化合物为N，N-二苯甲基芳基磺酰胺。