6-<(1,1-dimethylethoxy)carbonyl>-12-oxo-2,6,11-triazatetradecanedioic acid, 1-(1,1-dimethylethyl)-14-ethyl ester | 160677-43-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-<(1,1-dimethylethoxy)carbonyl>-12-oxo-2,6,11-triazatetradecanedioic acid, 1-(1,1-dimethylethyl)-14-ethyl ester
• 英文别名: 1-(1,1-Dimethylethyl) 14-ethyl 6-[(1,1-dimethylethoxy)carbonyl]-12-oxo-2,6,11-triazatetradecanedioate；ethyl 3-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butylamino]-3-oxopropanoate
• CAS: 160677-43-0
• 化学式: C₂₂H₄₁N₃O₇
• 分子量: 459.583
• InChiKey: WRBFTIHRYKZKQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-<(1,1-dimethylethoxy)carbonyl>-12-oxo-2,6,11-triazatetradecanedioic acid, 1-(1,1-dimethylethyl)-14-ethyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 25.5h， 生成 N-[4-(3-aminopropylamino)butyl]-N'-[6-(diaminomethylideneamino)hexyl]-N'-methylpropanediamide
  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 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 反应 48.5h， 生成 6-<(1,1-dimethylethoxy)carbonyl>-12-oxo-2,6,11-triazatetradecanedioic acid, 1-(1,1-dimethylethyl)-14-ethyl 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

文献信息

• 15-deoxyspergualin analogs, their method of preparation and their use in
  申请人：Fournier Industrie ET Sante

  公开号：US05476870A1

  公开（公告）日：1995-12-19

  The present invention relates, by way of novel industrial products, to compounds which are structurally related to 15-deoxyspergualin. These novel compounds have the formula ##STR1## in which: n is equal to 6 or 8 and A is a single bond, CH.sub.2, CHF, CH(OH), CH(OCH.sub.3), CH.sub.2 NH or CH.sub.2 O, and their addition salts.

  本发明涉及一种与15-去氧斯伯格林结构相关的化合物，作为新型工业产品。这些新型化合物的分子式为##STR1## 其中：n等于6或8，A是单键，CH.sub.2，CHF，CH（OH），CH（OCH.sub.3），CH.sub.2 NH或CH.sub.2 O，以及它们的加合盐。
• US5476870A
  申请人：——

  公开号：US5476870A

  公开（公告）日：1995-12-19
• Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety
  作者：Luc Lebreton、Jocelyne Annat、Philippe Derrepas、Patrick Dutartre、Patrice Renaut

  DOI：10.1021/jm980431g

  日期：1999.1.1

  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.