13-amino-3-[[(1,1-dimethylethoxy)carbonyl]-amino]-12-oxo-2,4,11-triazatridec-2-enoic acid,1,1-dimethylethyl ester

• 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: 13-amino-3-[[(1,1-dimethylethoxy)carbonyl]-amino]-12-oxo-2,4,11-triazatridec-2-enoic acid,1,1-dimethylethyl ester
• 英文别名: 1,1-Dimethylethyl 13-amino-3-[[(1,1-dimethylethoxy)carbonyl]amino]-12-oxo-2,4,11-triazatridec-2-enoate；13-Amino-3-[[(1,1-dimethylethoxy)carbonyl]-amino]-12-oxo-2,4,11-triazatridec-2-enoic acid, 1,1-dimethylethyl ester；tert-butyl N-[N'-[6-[(2-aminoacetyl)amino]hexyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• 化学式: C₁₉H₃₇N₅O₅
• 分子量: 415.533
• InChiKey: WOXKZRRFJUMOJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  13-amino-3-[[(1,1-dimethylethoxy)carbonyl]-amino]-12-oxo-2,4,11-triazatridec-2-enoic acid,1,1-dimethylethyl ester 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 <4-<(3-aminopropyl)amino>butoxycarbonylamino>-N-<6-<(aminoiminomethyl)amino>hexyl>acetamide 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：

  N,N'-bis-Boc-S-methyl-isothiourea 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 44.0h， 生成 13-amino-3-[[(1,1-dimethylethoxy)carbonyl]-amino]-12-oxo-2,4,11-triazatridec-2-enoic acid,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

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：US05637613A1

  公开（公告）日：1997-06-10

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

  本发明涉及一种与15-去氧斯佩尔瓜林结构相关的化合物，其具有以下式的结构：A为单键、基团--CH₂--、基团--CH₂O--、基团--CH₂NH--、基团--CH(OH)--、基团--CHF--或基团--CH(OCH₃)--，n等于6或8，以及它们的加合盐。这些新型化合物特别适用于免疫抑制剂。该发明还涉及制备上述化合物的方法。
• US5476870A
  申请人：——

  公开号：US5476870A

  公开（公告）日：1995-12-19
• US5637613A
  申请人：——

  公开号：US5637613A

  公开（公告）日：1997-06-10
• 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.