<(6-oxohexyl)carboimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester | 221249-70-3

• 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: <(6-oxohexyl)carboimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester
• 英文别名: tert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-N'-(6-oxohexyl)carbamimidoyl]carbamate
• CAS: 221249-70-3
• 化学式: C₁₇H₃₁N₃O₅
• 分子量: 357.45
• InChiKey: IPXJZGRBAVKOKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  <(6-oxohexyl)carboimidoyl>biscarbamic acid, bis(1,1-dimethylethyl) ester 在 sodium cyanoborohydride 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 2-[6-(diaminomethylideneamino)hexylamino]ethyl N-[4-(3-aminopropylamino)butyl]carbamate
  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：

  6-氨基-1-己醇 在 重铬酸吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 120.0h， 生成 <(6-oxohexyl)carboimidoyl>biscarbamic 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

文献信息

• PEPTIDE DERIVATIVES AND MEDICINAL COMPOSITIONS
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1275657A1

  公开（公告）日：2003-01-15

  An object of the present invention is to provide a novel nociceptin receptor agonist. The present invention relates to a peptide derivative represented by the following general formula (1):    (in which A represents alkylene, -(CH2)nCO- or a group represented by the following formula (2) or (3): wherein n represents an integer of 1 to 8; X and Y are same or different and each represents -CONH- or -CH2NH-; R1, R2 and R3 are same or different and each represents alkyl, aryl or heteroaryl; Z represents -CON(R4)R5 or -CH2N(R4)R5; and R4 and R5 are same or different and each represents hydrogen, alkyl, aryl or heteroaryl) or a pharmaceutically acceptable salt thereof. A pharmaceutical composition according to the present invention is useful as a nociceptin receptor agonist.

  本发明的目的是提供一种新型痛觉素受体激动剂。 本发明涉及一种由下式通式（1）代表的肽衍生物： (其中 A 代表亚烷基、-(CH2)nCO- 或下式(2)或(3)所代表的基团： 其中 n 代表 1 至 8 的整数；X 和 Y 相同或不同，各自代表-CONH-或-CH2NH-；R1、R2 和 R3 相同或不同，各自代表烷基、芳基或杂芳基；Z 代表-CON(R4)R5 或-CH2N(R4)R5；R4 和 R5 相同或不同，各自代表氢、烷基、芳基或杂芳基）或其药学上可接受的盐。 根据本发明的药物组合物可用作痛觉素受体激动剂。
• EP1275657
  申请人：——

  公开号：——

  公开（公告）日：——
• US7163921B1
  申请人：——

  公开号：US7163921B1

  公开（公告）日：2007-01-16
• 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.