2,4-Dioxo-9-t-butyl-1,5-dicyan-3-azaspiro<5.5>undecan | 97739-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 2,4-Dioxo-9-t-butyl-1,5-dicyan-3-azaspiro<5.5>undecan
• 英文别名: 9-tert-butyl-2,4-dioxo-3-aza-spiro[5.5]undecane-1,5-dicarbonitrile；9-tert-Butyl-1,5-dicyano-2,4-dioxo-3-azaspiro-[5.5 ]undecane；9-Tert-butyl-2,4-dioxo-3-azaspiro[5.5]undecane-1,5-dicarbonitrile
• CAS: 97739-31-6
• 化学式: C₁₆H₂₁N₃O₂
• 分子量: 287.362
• InChiKey: ATWJPFJHJILEGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  93.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-叔丁基环己酮 、 氰乙酸乙酯 在 氨 作用下， 以 sodium hydroxide 、 乙醇 为溶剂， 生成 2,4-Dioxo-9-t-butyl-1,5-dicyan-3-azaspiro<5.5>undecan
  参考文献：
  名称：

  Spiropiperidine derivatives and their use as fungicides

  摘要：

  这项发明提供了一般式的螺环哌啶衍生物或其酸盐加合物，其中R¹代表氢原子或可选择取代的烷基、芳基或芳基烷基；R²代表氢原子或可选择取代的烷基、烯基、炔基、环烷基、芳基、芳基烷基或杂环基；X代表-CH₂-的两个基团或X代表-O-的两个基团；它们的制备方法；含有这种化合物的组合物以及它们作为杀菌剂的用途。

  公开号：

  EP0621267A1

文献信息

• Chemical and electrocatalytic cascade cyclization of Guareschi imides: ‘one-pot’ simple and efficient way to the 2,4-dioxo-3-azabicyclo[3.1.0]hexane scaffold
  作者：Anatoly N. Vereshchagin、Michail N. Elinson、Evgeniya O. Dorofeeva、Dmitry V. Demchuk、Ivan S. Bushmarinov、Alexander S. Goloveshkin、Gennady I. Nikishin

  DOI：10.1016/j.tet.2013.04.035

  日期：2013.6

  as mediator results in fast and efficient cyclization with formation of a substituted 3-azabicyclo[3.1.0]hexane system in 80–98%. The fast (30 min) electrocatalytic reaction proceeds smoothly under neutral and mild conditions. The use of electrocatalysis in a cascade cyclization reaction is an efficient approach to the medicinally relevant 3-azabicyclo[3.1.0]hexane scaffold avoiding the inconvenient

  在存在溴化钠作为介体的情况下，在未分裂的细胞中，瓜尔基酰亚胺在乙醇中的电解可快速有效地环化，形成80-98％的取代的3-氮杂双环[3.1.0]己烷系统。快速（30分钟）的电催化反应在中性和温和条件下平稳进行。在级联环化反应中使用电催化是医学上有用的3-氮杂双环[3.1.0]己烷骨架的有效方法，避免了分子卤素或卤代底物直接使用的不便，并且从多样性导向的角度出发也是有益的大规模的过程。
• Spiropiperidine derivatives and their use as fungicides
  申请人：SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V.

  公开号：EP0621267A1

  公开（公告）日：1994-10-26

  The invention provides spiropiperidine derivatives of the general formula or an acid-addition salt thereof, in which R¹ represents a hydrogen atom or an optionally substituted alkyl, aryl or aralkyl group; R² represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl or heterocyclyl group; and either both groups X represent -CH₂- or both groups X represent -O-; processes for their preparation; compositions containing such compounds and their use as fungicides.

  这项发明提供了一般式的螺环哌啶衍生物或其酸盐加合物，其中R¹代表氢原子或可选择取代的烷基、芳基或芳基烷基；R²代表氢原子或可选择取代的烷基、烯基、炔基、环烷基、芳基、芳基烷基或杂环基；X代表-CH₂-的两个基团或X代表-O-的两个基团；它们的制备方法；含有这种化合物的组合物以及它们作为杀菌剂的用途。
• 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。
• US5436343A
  申请人：——

  公开号：US5436343A

  公开（公告）日：1995-07-25
• Antiarthritic and supressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents
  作者：Alison M. Badger、David A. Schwartz、Donald H. Picker、James W. Dorman、Fontaine C. Bradley、Elaine N. Cheeseman、Michael J. DiMartino、Nabil Hanna、Christopher K. Mirabelli

  DOI：10.1021/jm00173a010

  日期：1990.11

  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.