4-[[(3,5-Difluorophenyl)methyl-pyridin-3-ylamino]methyl]-2-(2-methylphenyl)benzoic acid | 478909-23-8

• 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-[[(3,5-Difluorophenyl)methyl-pyridin-3-ylamino]methyl]-2-(2-methylphenyl)benzoic acid
• CAS: 478909-23-8
• 化学式: C₂₇H₂₂F₂N₂O₂
• 分子量: 444.481
• InChiKey: YBXDMPVIWDDQBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[[(3,5-Difluorophenyl)methyl-pyridin-3-ylamino]methyl]-2-(2-methylphenyl)benzoic acid 在 lithium hydroxide 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-[4-N-3,5-difluorobenzyl-N-(3-pyridyl)aminomethyl-2-(2-methylphenyl)-benzoyl]methionine
  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：

  3,5-二氟苯甲醛 在 sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 甲苯 为溶剂， 反应 11.5h， 生成 4-[[(3,5-Difluorophenyl)methyl-pyridin-3-ylamino]methyl]-2-(2-methylphenyl)benzoic 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