(S)-2-{[4-Butyl-2'-methyl-5-(pyridin-3-yloxymethyl)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid methyl ester | 191105-14-3

• 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-Butyl-2'-methyl-5-(pyridin-3-yloxymethyl)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid methyl ester
• CAS: 191105-14-3
• 化学式: C₃₀H₃₆N₂O₄S
• 分子量: 520.693
• InChiKey: LYUNYXDAAQPPHE-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.0
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  77.52
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-2-{[4-Butyl-2'-methyl-5-(pyridin-3-yloxymethyl)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (S)-2-{[4-Butyl-2'-methyl-5-(pyridin-3-yloxymethyl)-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：

  methyl 2-(2-methylphenyl)-4-(3-pyridyloxymethyl)-5-iodobenzoate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium hydroxide 、 potassium carbonate 、 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 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (S)-2-{[4-Butyl-2'-methyl-5-(pyridin-3-yloxymethyl)-biphenyl-2-carbonyl]-amino}-4-methylsulfanyl-butyric acid methyl ester
  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