4-tert.-Butyl-cyclohexan-diessigsaeure-(1,1)-anhydrid | 93807-74-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4-tert.-Butyl-cyclohexan-diessigsaeure-(1,1)-anhydrid
• 英文别名: (4-tert-butyl-cyclohexane-1,1-diyl)-bis-acetic acid anhydride；9-tert-butyl-3-oxa-spiro[5.5]undecane-2,4-dione；9-Tert-butyl-3-oxaspiro[5.5]undecane-2,4-dione
• CAS: 93807-74-0
• 化学式: C₁₄H₂₂O₃
• 分子量: 238.327
• InChiKey: KGOOZLLOQNXAJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-tert.-Butyl-cyclohexan-diessigsaeure-(1,1)-anhydrid 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 [3-(9-tert-butyl-3-aza-spiro[5.5]undec-3-yl)-propyl]-dimethyl-amine
  参考文献：
  名称：

  Antiarthritic and supressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents

  摘要：

  Spirogermanium (1; 8,8-diethyl-N,N-dimethyl-2-aza-8- germaspiro[4.5]decane-2-propanamine dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride (9) as a more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p less than 0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.

  DOI：

  10.1021/jm00173a010
• 作为产物：
  描述：

  2,4-Dioxo-9-t-butyl-1,5-dicyan-3-azaspiro<5.5>undecan 在 盐酸 、 水 、 乙酸酐 、 溶剂黄146 作用下， 反应 88.0h， 生成 4-tert.-Butyl-cyclohexan-diessigsaeure-(1,1)-anhydrid
  参考文献：
  名称：

  Antiarthritic and supressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents

  摘要：

  Spirogermanium (1; 8,8-diethyl-N,N-dimethyl-2-aza-8- germaspiro[4.5]decane-2-propanamine dihydrochloride) is a potent cytotoxic agent in vitro which has demonstrated limited activity in experimental animal tumor models. Subsequently, it has been reported that spirogermanium has antiarthritic and suppressor cell-inducing activity. We have synthesized a series of substituted 8-hetero-2-azaspiro[4.5]decane and 9-hetero-3-azaspiro[5.5]undecane analogues of spirogermanium to identify the heteroatom requirements for in vivo antiarthritic and suppressor cell-inducing activity. This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active. Following the identification of N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride (9) as a more active analogue than spirogermanium, a series of 8,8-dipropyl analogues with various amine substituents were synthesized. A number of these analogues had activity similar to that of 9. A correlation between activity in the adjuvant arthritic rat and the ability to induce suppressor cells (r = 0.894, p less than 0.001) suggests an association between the two pharmacologic effects. While the precise biochemical mechanism(s) for the pharmacological activity is unclear, these data suggest that compounds within this series, e.g., N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride, may provide effective therapy in diseases of autoimmune origin and/or the prevention of rejection in tissue transplantation.

  DOI：

  10.1021/jm00173a010

文献信息

• [EN] 4-T-BUTYLGABAPENTIN AND ITS SYNTHESIS<br/>[FR] 4-T-BUTYLGABAPENTINE ET SYNTHESE DE CE COMPOSE
  申请人：HIKAL LTD

  公开号：WO2005087709A1

  公开（公告）日：2005-09-22

  The present invention relates to compounds cis (Z) and trans (E) stereoisomers of 4-t-butylgapentin of formula (11) and (12) and a process for the preparation of the said stereoisomers.

  本发明涉及公式（11）和（12）的4-叔丁基加巴喷丁的顺式（Z）和反式（E）立体异构体化合物以及所述立体异构体的制备方法。
• Gabapentin analogues and process thereof
  申请人：Kuppuswamy Nagarajan

  公开号：US20050209332A1

  公开（公告）日：2005-09-22

  The present invention relates to compounds cis (Z) and trans (E) stereoisomers of 4-t-butylgabapentin of formula (11) and (12) and a process for the preparation of the said stereoisomers.

  本发明涉及化合物4-叔丁基加巴喷丁的顺式（Z）和反式（E）立体异构体，化学式为（11）和（12），以及制备所述立体异构体的方法。
• Nouveaux derivés d'acides alcenecarboxyliques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0570263A1

  公开（公告）日：1993-11-18

  Composés de formule (I) : dans laquelle : R₁ et R₂identiques ou différents représentent un radical alkyle (C₁-C₆) linéaire ou ramifié, un radical phényle substitué ou non, un radical pyridinyl, un radical thiényl, ou forment, avec l'atome de carbone auxquels ils sont attachés, un cycle cycloalkyle (C₄-C₇) substitué ou non, R₃représente un radical phénylsulfonyl substitué ou non, un radical alkyle (C₁-C₆) linéaire ou ramifié, un radical alkylaminocarbonyl, ou un radical acyle (C₁-C₆) linéaire ou ramifié, R₄représente l'un quelconque des radicaux :         -CH=CH-(CH₂)p-CO₂H  ou   -CH₂-CH₂-(CH₂)p-CO₂H dans lesquels p est égal à 0, 1, 2 ou 3, n et midentiques ou différents représentent 0, 1 ou 2, leurs isomères, énantiomères, diastéréoisomères et épimères ainsi que leurs sels d'addition à un acide ou à une base pharmaceutiquement acceptable. Les composés décrits dans la présente invention possèdent des propriétés antithromboxane A₂ aussi bien en tant qu'antagonistes des récepteurs au thromboxane A₂ (TXA₂) qu'en tant qu'inhibiteurs de l'activité de l'enzyme responsable de la synthèse du thromboxane A₂: la thromboxane A₂-synthase.

  式(I)化合物： 其中 ： R₁和 R₂可以相同或不同，代表直链或支链烷基（C₁-C₆）、取代或未取代的苯基、吡啶基、噻吩基、 或与所连接的碳原子形成取代或未取代的环烷基（C₄-C₇）环、 R₃ 代表 一个取代或未取代的苯磺酰基 直链或支链烷基 (C₁-C₆) 烷基氨基羰基 或直链或支链酰基（C₁-C₆）、 R₄ 代表......中的任一个基团： -CH=CH-(CH₂)p-CO₂H 或 -CH₂-CH₂-(CH₂)p-CO₂H 其中 p 等于 0、1、2 或 3、 n 和 mid 相同或不同，代表 0、1 或 2、 它们的异构体、对映体、非对映异构体和表聚物，以及它们与药学上可接受的酸或碱的加成盐。 本发明所述化合物具有抗血栓素 A₂的特性，既是血栓素 A₂受体拮抗剂（TXA₂），又是血栓素 A₂合成酶（血栓素 A₂-合成酶）活性的抑制剂。
• Spiranes. III.^1a,b Azaspiranes and Intermediates^1c
  作者：Leonard M. Rice、Charles F. Geschickter、Charles H. Grogan

  DOI：10.1021/jm00340a012

  日期：1963.7
• US5436343A
  申请人：——

  公开号：US5436343A

  公开（公告）日：1995-07-25