{4-[Benzyl-(3-tert-butoxycarbonylamino-pentyl)-amino]-butylcarbamoyloxy}-acetic acid methyl ester | 252353-66-5

• 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-[Benzyl-(3-tert-butoxycarbonylamino-pentyl)-amino]-butylcarbamoyloxy}-acetic acid methyl ester
• CAS: 252353-66-5
• 化学式: C₂₅H₄₁N₃O₆
• 分子量: 479.617
• InChiKey: QIQMBHYREOBVOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.86
• 重原子数：
  34.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  106.2
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {4-[Benzyl-(3-tert-butoxycarbonylamino-pentyl)-amino]-butylcarbamoyloxy}-acetic acid methyl ester 在 palladium dichloride N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 为溶剂， -30.0~20.0 ℃ 、101.33 kPa 条件下， 反应 23.5h， 生成 [4-(3-Amino-pentylamino)-butyl]-carbamic acid (6-guanidino-hexylcarbamoyl)-methyl ester
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 2. Structural Modifications of the Spermidine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine "D" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene a to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60e which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm991043x
• 作为产物：
  描述：

  4-[Benzyl(3-hydroxypentyl)amino]butanenitrile 在 palladium on activated charcoal 、 镍 sodium azide 、 氨 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 甲苯 为溶剂， 20.0~80.0 ℃ 、600.0 kPa 条件下， 反应 61.0h， 生成 {4-[Benzyl-(3-tert-butoxycarbonylamino-pentyl)-amino]-butylcarbamoyloxy}-acetic acid methyl ester
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 2. Structural Modifications of the Spermidine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine "D" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene a to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60e which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm991043x