3-<(1,1-dimethylethoxy)carbonylamino>-21-<(1,1-dimethylethoxy)carbonyl>-12,15-dioxo-14-thia-2,4,11,16,21,25-hexaazahexacos-2-enedioic acid, bis(1,1-dimethylethyl) ester | 221249-44-1

• 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: 3-<(1,1-dimethylethoxy)carbonylamino>-21-<(1,1-dimethylethoxy)carbonyl>-12,15-dioxo-14-thia-2,4,11,16,21,25-hexaazahexacos-2-enedioic acid, bis(1,1-dimethylethyl) ester
• 英文别名: tert-butyl N-[4-[[2-[6-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]hexylamino]-2-oxoethyl]sulfanylcarbonylamino]butyl]-N-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]carbamate
• CAS: 221249-44-1
• 化学式: C₃₇H₆₉N₇O₁₀S
• 分子量: 804.062
• InChiKey: DRADLCNIFAYXPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  55
• 可旋转键数：
  29
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  240
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 3-<(1,1-dimethylethoxy)carbonylamino>-21-<(1,1-dimethylethoxy)carbonyl>-12,15-dioxo-14-thia-2,4,11,16,21,25-hexaazahexacos-2-enedioic acid, bis(1,1-dimethylethyl) ester 以 二氯甲烷 为溶剂， 反应 24.0h， 以77%的产率得到<4-<(3-aminopropyl)amino>butyl>carbamothioic acid, S-<2-<6-(aminoiminomethylamino)hexyl>amino>-2-oxoethyl ester, tris(trifluoroacetate)
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm980431g
• 作为产物：
  描述：

  O,O'-Di(tert-butyl)-N-<4-(mesyloxy)butyl>-N,N'-(propan-1,3-diyl)bis 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 3-<(1,1-dimethylethoxy)carbonylamino>-21-<(1,1-dimethylethoxy)carbonyl>-12,15-dioxo-14-thia-2,4,11,16,21,25-hexaazahexacos-2-enedioic acid, bis(1,1-dimethylethyl) ester
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm980431g