[3-(8,8-dimethyl-2-aza-8-sila-spiro[4.5]dec-2-yl)-propyl]-dimethyl-amine | 41992-03-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [3-(8,8-dimethyl-2-aza-8-sila-spiro[4.5]dec-2-yl)-propyl]-dimethyl-amine
• 英文别名: 3-(8,8-dimethyl-2-aza-8-silaspiro[4.5]decan-2-yl)-N,N-dimethylpropan-1-amine
• CAS: 41992-03-4
• 化学式: C₁₅H₃₂N₂Si
• 分子量: 268.518
• InChiKey: MQYGEGPEKLWUME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  Cyano-(4-cyano-1,1-dimethyl-silinan-4-yl)-acetic acid ethyl ester 在 盐酸 、 lithium aluminium tetrahydride 、 水 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 反应 91.0h， 生成 [3-(8,8-dimethyl-2-aza-8-sila-spiro[4.5]dec-2-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

文献信息

• Spirans XXI. Synthesis of silaazaspiro[4.5]decanes and silaazaspiro[5.5]undecanes
  作者：Leonard M. Rice、Bhagvandas S. Sheth、James W. Wheeler

  DOI：10.1002/jhet.5570100510

  日期：1973.10

  N-(2-Dimethylaminopropyl)-8,8-dimethyl-8-sila-2-azaspiro[4.5]decane (1) and N-(3-dimethyl-aminopropyl)-9,9-dimethyl-9-sila-3-azaspiro[5.5]undecane (2) have been synthesized from 4,4-dimethyl-4-silacyclohexanone (5). Biological evaluation of 1 and 2 indicated cytotoxic action against human cancer cells grown in tissue culture.

  N-（2-二甲基氨基丙基）-8,8-二甲基-8-sila-2-azaspiro [4.5]癸烷（1）和N-（3-二甲基氨基丙基）-9,9-二甲基-9-sila-3由4，4-二甲基-4-硅环己酮（5）合成了-azaspiro [5.5]十一烷（2）。对1和2的生物学评估表明，它对组织培养中生长的人类癌细胞具有细胞毒作用。
• 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.