methyl (2S)-4-methylsulfanyl-2-[(4-nitrobenzoyl)amino]butanoate | 61315-66-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-4-methylsulfanyl-2-[(4-nitrobenzoyl)amino]butanoate
• CAS: 61315-66-0
• 化学式: C₁₃H₁₆N₂O₅S
• mdl: MFCD00813534
• 分子量: 312.346
• InChiKey: JVHCJGKDVFLBER-NSHDSACASA-N

物化性质

• 沸点：
  540.1±50.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S)-4-methylsulfanyl-2-[(4-nitrobenzoyl)amino]butanoate 在 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以88%的产率得到N-(4-aminobenzoyl)-L-methionine methyl ester
  参考文献：
  名称：

  法呢基转移酶新型模块化双底物类似物抑制剂的设计、合成和评价。

  摘要：

  可以从法呢基转移酶抑制剂开发用于治疗癌症的有前景的潜在化学疗法。提出了一类新的模块化双底物法呢基转移酶抑制剂，可以直接合成。这种抑制剂的一个例子是化合物 1，其 IC50 值为 3.7 μM。

  DOI：

  10.1002/(sici)1521-3773(19990712)38:13/14<2032::aid-anie2032>3.0.co;2-d
• 作为产物：
  描述：

  L-蛋氨酸甲酯盐酸盐 、 4-硝基苯甲酰氯 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以90%的产率得到methyl (2S)-4-methylsulfanyl-2-[(4-nitrobenzoyl)amino]butanoate
  参考文献：
  名称：

  法呢基转移酶新型模块化双底物类似物抑制剂的设计、合成和评价。

  摘要：

  可以从法呢基转移酶抑制剂开发用于治疗癌症的有前景的潜在化学疗法。提出了一类新的模块化双底物法呢基转移酶抑制剂，可以直接合成。这种抑制剂的一个例子是化合物 1，其 IC50 值为 3.7 μM。

  DOI：

  10.1002/(sici)1521-3773(19990712)38:13/14<2032::aid-anie2032>3.0.co;2-d

文献信息

• Design, Synthesis, and Evaluation of Novel Modular Bisubstrate Analogue Inhibitors of Farnesyltransferase
  作者：Martin Schlitzer、Isabel Sattler

  DOI：10.1002/(sici)1521-3773(19990712)38:13/14<2032::aid-anie2032>3.0.co;2-d

  日期：1999.7.12

  Promising potential chemotherapeutics for the treatment of cancer can be developed from farnesyltransferase inhibitors. A novel class of modular bisubstrate farnesyltransferase inhibitors is presented that can be synthesized in a straightforward manner. An example of such an inhibitor is compound 1, which has an IC50 value of 3.7 μM.

  可以从法呢基转移酶抑制剂开发用于治疗癌症的有前景的潜在化学疗法。提出了一类新的模块化双底物法呢基转移酶抑制剂，可以直接合成。这种抑制剂的一个例子是化合物 1，其 IC50 值为 3.7 μM。
• Synthesis and evaluation of homofarnesoyl-substituted CAAX-peptidomimetics as farnesyltransferase inhibitors and antiproliferative agents
  作者：Martin Schlitzer、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1016/s0968-0896(99)00165-0

  日期：1999.9

  Several CAAX-peptidomimetics were linked to homofarnesoic acid via a beta-alanyl spacer with the intention to obtain a novel type of bisubstrate analogue farnesyltransferase inhibitors. However, the compounds were found to be only weakly active in the farnesyltransferase inhibition assay. Nevertheless, they displayed antiproliferative activity against different tumor cell lines in the low micromolar range. Replacement of the beta-alanine moiety by aspartic acid-1-methyl ester resulted in a compound which inhibited the farnesyltransferase with an IC50 of 860 nM. The corresponding free acid showed a eightfold loss in activity (IC50 = 6.9 microM).
• Design, synthesis and early structure–activity relationship of farnesyltransferase inhibitors which mimic both the peptidic and the prenylic substrate
  作者：Martin Schlitzer、Markus Böhm、Isabel Sattler、Hans-Martin Dahse

  DOI：10.1016/s0968-0896(00)00138-3

  日期：2000.8

  Inhibition of the farnesylation of ras proteins has been identified as a promising target in tumor therapy. Only a few farnesyltransferase inhibitors are bisubstrate analogues displaying features of both substrates, the farnesylpyrophosphate and the C-terminal CAAX-tetrapeptide sequence of the res protein. These known bisubstrate analogues consist of an AAX-tripeptide and a farnesyl residue connected through various linkers. We have developed a class of novel compounds that mimic a bisubstrate inhibitor structure and that differ from the known ones by lacking peptidic or farnesylic substructures. Long chain fatty acids and aryl-substituted carboxylic acids were used as farnesyl surrogates. These structures were linked to isoleucine amide, benzoic acid amide, N-substituted aminobenzenesulfonamides and N-alpha-aryl-substituted methionine derivatives, respectively, which function as AA- or AAX-mimetics. (C) 2000 Elsevier Science Ltd. All rights reserved.