methyl (2S)-2-[[4-[[N-[(3,5-difluorophenyl)methyl]anilino]methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate | 216239-04-2

• 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: methyl (2S)-2-[[4-[[N-[(3,5-difluorophenyl)methyl]anilino]methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 216239-04-2
• 化学式: C₃₄H₃₄F₂N₂O₃S
• 分子量: 588.718
• InChiKey: OSCRTSBTFQJXNC-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[4-[[N-[(3,5-difluorophenyl)methyl]anilino]methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (S)-2-[(5-{[(3,5-Difluoro-benzyl)-phenyl-amino]-methyl}-2'-methyl-biphenyl-2-carbonyl)-amino]-4-methylsulfanyl-butyric acid
  参考文献：
  名称：

  Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy

  摘要：

  The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumorderived cell line.

  DOI：

  10.1021/jm9901935
• 作为产物：
  描述：

  (3,5-Difluoro-benzyl)-phenyl-amine 在 sodium hydroxide 、 正丁基锂 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 methyl (2S)-2-[[4-[[N-[(3,5-difluorophenyl)methyl]anilino]methyl]-2-(2-methylphenyl)benzoyl]amino]-4-methylsulfanylbutanoate
  参考文献：
  名称：

  Second-Generation Peptidomimetic Inhibitors of Protein Farnesyltransferase Demonstrating Improved Cellular Potency and Significant in Vivo Efficacy

  摘要：

  The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumorderived cell line.

  DOI：

  10.1021/jm9901935