N-(6-cyanohexanoyl)glycine | 185247-97-6

• 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: N-(6-cyanohexanoyl)glycine
• 英文别名: N-(6-cyanohexanoyl)-glycine；2-(6-cyanohexanoylamino)acetic acid
• CAS: 185247-97-6
• 化学式: C₉H₁₄N₂O₃
• 分子量: 198.222
• InChiKey: GWRLVNZCMYLYSS-UHFFFAOYSA-N

物化性质

• 沸点：
  514.5±35.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-cyanohexanoyl)glycine 在 palladium on activated charcoal 、 镍 sodium hydroxide 、 二苯基膦叠氮化物 、 氢气 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 25.0 ℃ 、350.0 kPa 条件下， 反应 37.75h， 生成 22-amino-6-<(1,1-dimethylethoxy)carbonyl>-12,16-dioxo-11-oxa-2,6,13,15-tetraaza-docosanoic 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
• 作为产物：
  描述：

  N-(6-bromohexanoyl)glycine, ethyl ester 在 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 16.0h， 生成 N-(6-cyanohexanoyl)glycine
  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：US05733928A1

  公开（公告）日：1998-03-31

  The present invention relates to a novel compound selected from the group consisting of: (i) the compounds of the formula ##STR1## in which: A is a group --CO--NH-- or a group --NH--CO--, R is a hydrogen atom or a methyl group, and *C, if R is not the hydrogen atom, is an asymmetric carbon of (R,S) or (R) configuration; and (ii) their addition salts. It further relates to the method of preparing this compound and to its use in therapeutics.

  本发明涉及从以下组合中选取的一种新化合物：(i) 公式 ##STR1## 中的化合物，其中：A是一个基团--CO--NH--或一个基团--NH--CO--，R是氢原子或甲基基团，*C，如果R不是氢原子，则是(R,S)或(R)构型的不对称碳原子；以及(ii)它们的加合盐。它还涉及制备该化合物的方法以及其在治疗中的应用。
• Analogues de la 15-déoxyspergualine, leur procédé de préparation et leur utilisation en thérapeutique
  申请人：FOURNIER INDUSTRIE ET SANTE

  公开号：EP0743300A1

  公开（公告）日：1996-11-20

  La présente invention concerne un nouveau composé qui est choisi parmi l'ensemble constitué par : (i) les composés de formule : dans laquelle :    A représente un groupe -CO-NH- ou un groupe -NH-CO-,    R représente un atome d'hydrogène ou un groupe méthyle,    *C représente, lorsque R n'est pas l'atome d'hydrogène, un carbone asymétrique de configuration (R,S) ou (R), et (ii) leurs sels d'addition Elle concerne également le procédé de préparation et l'utilisation en thérapeutique de ce composé.

  本发明涉及一种新化合物，该化合物选自以下组别：......： (i) 式......化合物 其中： A 代表基团-CO-NH- 或基团-NH-CO-、 R 代表氢原子或甲基、 *当 R 不是氢原子时，C 代表（R,S）或（R）构型的不对称碳，以及 (ii) 它们的加成盐 还涉及该化合物的制备工艺和治疗用途。
• US5733928A
  申请人：——

  公开号：US5733928A

  公开（公告）日：1998-03-31
• 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.