4-(bromomethyl)-α,α-difluorobenzeneacetic acid 1,1-dimethylethyl ester | 127152-63-0

• 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-(bromomethyl)-α,α-difluorobenzeneacetic acid 1,1-dimethylethyl ester
• 英文别名: α-(4-bromomethylphenyl)-α,α-difluoroacetic acid tert-butyl ester；1,1-dimethylethyl 2-(4-bromomethylphenyl)-2,2-difluoroacetate；tert-Butyl 2,2-Difluoro-2-(4-bromomethylphenyl)acetate；tert-butyl 2-[4-(bromomethyl)phenyl]-2,2-difluoroacetate
• CAS: 127152-63-0
• 化学式: C₁₃H₁₅BrF₂O₂
• 分子量: 321.162
• InChiKey: DWSZILVHMKMBPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(bromomethyl)-α,α-difluorobenzeneacetic acid 1,1-dimethylethyl ester 在 钯 氢气 、 碳酸氢钠 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 六甲基磷酰三胺 、 水 为溶剂， 反应 23.5h， 生成 N-Fmoc-4-(tert-butoxycarbonyl-difluoro-methyl)-L-phenylalanine
  参考文献：
  名称：

  Synthesis of Fmoc-protected 4-carboxydifluoromethyl-L-phenylalanine: A phosphotyrosyl mimetic of potential use for signal transduction studies

  摘要：

  4-(Carboxymethyl)phenylalanine (2) and its alpha,alpha-difluoro homologue 4-(carboxydifluoromethyl)-phenylalanine (3) have been described as phosphotyrosyl mimetics. Herein we report the synthesis of N-Fmoc 4-(0-tert-butyl carboxymethyl)-phenylalanine (4) and N-Fmoc 4-(0-tert-butyl carboxydifluoromethyl)phenylalanine (5) in high enantiomeric purity. These analogues bear orthogonal protection suitable for the preparation of inhibitors directed against a variety of signal transduction pathways, including SH2 and PTP domains and protein-tyrosine phosphatases. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(99)00076-9
• 作为产物：
  描述：

  α-(4-methylphenyl)-α-oxoacetic acid tert-butyl ester 在 N-溴代丁二酰亚胺(NBS) 、 二乙胺基三氟化硫 、 (PhCOO)2O 作用下， 以 四氯化碳 为溶剂， 生成 4-(bromomethyl)-α,α-difluorobenzeneacetic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Synthesis of Fmoc-protected 4-carboxydifluoromethyl-L-phenylalanine: A phosphotyrosyl mimetic of potential use for signal transduction studies

  摘要：

  4-(Carboxymethyl)phenylalanine (2) and its alpha,alpha-difluoro homologue 4-(carboxydifluoromethyl)-phenylalanine (3) have been described as phosphotyrosyl mimetics. Herein we report the synthesis of N-Fmoc 4-(0-tert-butyl carboxymethyl)-phenylalanine (4) and N-Fmoc 4-(0-tert-butyl carboxydifluoromethyl)phenylalanine (5) in high enantiomeric purity. These analogues bear orthogonal protection suitable for the preparation of inhibitors directed against a variety of signal transduction pathways, including SH2 and PTP domains and protein-tyrosine phosphatases. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(99)00076-9

文献信息

• Carboxylic acids and tetrazoles as isosteric replacements for sulfate in cholecystokinin analogs
  作者：Jefferson W. Tilley、Waleed Danho、Kathleen Lovey、Rolf Wagner、Joseph Swistok、Raymond Makofske、Joseph Michalewsky、Joseph Triscari、David Nelson、Sally Weatherford

  DOI：10.1021/jm00107a037

  日期：1991.3

  A series of analogues of the satiety-inducing peptide cholecystokinin (CCK-8) was prepared in which the sulfated tyrosine required for activation of peripheral receptors was replaced with a carboxy(alkyl)- or tetrazolyl(alkyl)-phenylalanine to investigate whether an organic acid could serve the role of the sulfate group at the receptor. The necessary intermediates were prepared by previously reported

  制备了一系列诱导饱腹感的肽胆囊收缩素（CCK-8）的类似物，其中活化外围受体所需的硫酸化酪氨酸被羧基（烷基）-或四唑基（烷基）-苯丙氨酸替代，以研究是否有机酸可以充当受体上的硫酸根基团。必要的中间体是通过以前报道的方法或通过将羧基（烷基）或四唑基（烷基）苯基甲基溴与甘氨酸衍生的阴离子烷基化，然后进行保护基操作而制备的，并将这些中间体掺入乙酰基CCK-7衍生物中采用固相合成。在CCK结合试验中，使用均质的大鼠胰膜作为受体源，评估肽类似物对外周（CCK-A）受体的亲和力，或使用牛纹状体作为受体源，评估对中枢（CCK-B）受体的亲和力。进一步评估了它们在腹膜内注射后对大鼠食物摄入的影响。报道的许多化合物在CCK-A受体结合测定中均具有活性，尽管其效力不如乙酰基-CCK-7，并且可以减少食物摄入量，且效力可与乙酰基-CCK-7媲美。在旨在评估食欲抑制活性的膳食喂养模型中，乙酰基-CCK-7的ED50为7
• 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。
• Analogs of tyrosine sulfate or tyrosine phosphate containing peptides
  申请人：Hoffmann-La Roche Inc.

  公开号：US05182263A1

  公开（公告）日：1993-01-26

  Analogs of Tyrosine Sulfate or Tyrosine Phosphate containing peptides, the novel intermediate compounds used in the preparation of these analogs, as well as a method for suppressing appetite in subjects by administering to the subject an effective amount of CCK analog wherein one or more of any Tyrosine Sulfate present is substituted with a radical of the invention.

  含有酪氨酸硫酸盐或酪氨酸磷酸盐的肽类类似物，用于制备这些类似物的新型中间化合物，以及通过向受试者投与有效量的CCK类似物来抑制食欲的方法，其中任何存在的酪氨酸硫酸盐被本发明的基团所取代。
• Phosphonic and carboxylic acid derivatives as inhibitors of protein tyrosine phosphatase-1B (PTP-1B)
  申请人：Merck Frosst Canada & Co.

  公开号：US06365592B1

  公开（公告）日：2002-04-02

  The invention encompasses compounds represented by formula I: as well as compositions and methods of treatment. The compounds are inhibitors of the PTP-1B enzyme.

  本发明涵盖了由公式I代表的化合物，以及其治疗用途的组成物和方法。这些化合物是PTP-1B酶的抑制剂。
• Tyr-peptide analogs
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0339549A2

  公开（公告）日：1989-11-02

  Analogs of tyrosine sulfate- or tyrosine phosphate residue(s) containing peptides, the novel intermediate compounds used in the preparation of these analogs, as well as a method for suppressing appetite in subjects by administering to the subject an effective amount of CCK analog wherein one or more of any tyrosine sulfate residue(s) present is/are replaced by a residue of the invention.

  含酪氨酸硫酸盐或酪氨酸磷酸残基的多肽类似物、用于制备这些类似物的新型中间化合物，以及通过向受试者施用有效量的CCK类似物来抑制受试者食欲的方法，其中存在的一个或多个酪氨酸硫酸盐残基被本发明的残基取代。