(S)-2-(4-Amino-benzenesulfonylamino)-4-methylsulfanyl-butyric acid methyl ester | 250697-56-4

• 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: (S)-2-(4-Amino-benzenesulfonylamino)-4-methylsulfanyl-butyric acid methyl ester
• CAS: 250697-56-4
• 化学式: C₁₂H₁₈N₂O₄S₂
• 分子量: 318.418
• InChiKey: OJFOICMMZKWUAJ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.84
• 重原子数：
  20.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  98.49
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-2-(4-Amino-benzenesulfonylamino)-4-methylsulfanyl-butyric acid methyl ester 在 N-甲基吗啉 、 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 氯甲酸异丁酯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 methyl (2S)-4-methylsulfanyl-2-[[4-[3-[[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoyl]amino]propanoylamino]phenyl]sulfonylamino]butanoate
  参考文献：
  名称：

  Synthesis and evaluation of homofarnesoyl-substituted CAAX-peptidomimetics as farnesyltransferase inhibitors and antiproliferative agents

  摘要：

  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).

  DOI：

  10.1016/s0968-0896(99)00165-0
• 作为产物：
  描述：

  L-蛋氨酸甲酯盐酸盐 在 N-甲基吗啉 、 tin(ll) chloride 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 (S)-2-(4-Amino-benzenesulfonylamino)-4-methylsulfanyl-butyric acid methyl ester
  参考文献：
  名称：

  Different Amino Acid Replacements in CAAX-Tetrapeptide Based Peptidomimetic Farnesyltransferase Inhibitors

  摘要：

  In a series of CAAX-tetrapeptide based farnesyltransferase inhibitors it has been shown that the central AA-dipeptide can be replaced by tranexamic acid, 4-aminobenzenesulfonic acid, and 3-amino-N-(2,3-dimethylphenyl)benzenesulfonamide, respectively, yielding inhibitors active in the low micromolar range. Lipophilic derivatives of these compounds showed moderate anti-proliferative activity against different tumor cell lines. A promising class of peptidomimetic farnesyltransferase inhibitors was discovered through the replacement of the terminal AAX motif of the CAAX-tetrapeptide by 2-acylamino-5-aminobenzophenones.

  DOI：

  10.1002/(sici)1521-4184(19994)332:4<124::aid-ardp124>3.0.co;2-g

文献信息

• 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.