9,9-Dipropyl-3-oxa-spiro[5.5]undecane-2,4-dione | 123018-69-9

• 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: 9,9-Dipropyl-3-oxa-spiro[5.5]undecane-2,4-dione
• 英文别名: 4,4-Dipropylcyclohexane-1,1-diacetic acid anhydride；9,9-dipropyl-3-oxaspiro[5.5]undecane-2,4-dione
• CAS: 123018-69-9
• 化学式: C₁₆H₂₆O₃
• 分子量: 266.381
• InChiKey: YNXQLABCTIAIGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 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：

  9,9-Dipropyl-3-oxa-spiro[5.5]undecane-2,4-dione 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 [3-(9,9-Dipropyl-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：

  4,4-双丙基环己酮 在 palladium on activated charcoal 盐酸 、 氨 、 水 、 氢气 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 12.5h， 生成 9,9-Dipropyl-3-oxa-spiro[5.5]undecane-2,4-dione
  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

• Immunomodulatory azaspiranes
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0310321B1

  公开（公告）日：1994-11-30
• BADGER, ALISON M.;CHEESEMAN, ELAINE N.;DIMARTINO, MICHAEL J.;DORMAN, JAME+
  作者：BADGER, ALISON M.、CHEESEMAN, ELAINE N.、DIMARTINO, MICHAEL J.、DORMAN, JAME+

  DOI：——

  日期：——
• IMMUNOMODULATORY AZASPIRANES
  申请人：AnorMED Inc.

  公开号：EP0587800B1

  公开（公告）日：2003-04-02
• EP0609335A4
  申请人：——

  公开号：EP0609335A4

  公开（公告）日：1994-10-12
• METHODS FOR THE TREATMENT OF HYPERLIPIDEMIA USING AZASPIRANES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0609335A1

  公开（公告）日：1994-08-10