spiro[5.6]dodecan-3-one | 130065-92-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: spiro[5.6]dodecan-3-one
• CAS: 130065-92-8
• 化学式: C₁₂H₂₀O
• 分子量: 180.29
• InChiKey: KVQVBEZGTFSTFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  spiro[5.6]dodecan-3-one 在 乙酸铵 、 盐酸 、 水 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 93.0h， 生成 2-(3-Dimethylamino-propyl)-2-aza-dispiro[4.2.6.2]hexadecane-1,3-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
• 作为产物：
  描述：

  环庚烷甲醛 在 三乙基硅烷 、 硫酸 、 palladium dichloride 作用下， 以 苯 为溶剂， 反应 9.0h， 生成 spiro[5.6]dodecan-3-one
  参考文献：
  名称：

  分子动力学模拟定向合理设计靶向甲型流感病毒 M2 耐药突变体的抑制剂

  摘要：

  甲型流感病毒 M2 (A/M2) 在病毒膜中形成同源四聚体质子选择性通道。一直是金刚烷胺、金刚乙胺等抗病毒药物的药物靶点。然而，目前的大多数甲型流感病毒都在药物结合位点旁边携带耐药突变，如 S31N、V27A 和 L26F 等，每一种都可能在给定的流感季节占主导地位。在这些突变中，V27A 突变在药物选择压力下的传染性病毒中普遍存在。到目前为止，尽管经过多年广泛的药物化学研究和高通量筛选，V27A 还没有被小分子抑制剂成功靶向。以药物结合的分子动力学 (MD) 模拟和药物结合对早期实验研究中 A/M2 动力学的影响为指导，我们设计了一系列有效的螺胺抑制剂，不仅针对 WT，还针对 A/M2-27A 和 L26F 突变体，其 IC(50) 与金刚烷胺对 WT 通道的抑制相似。这些抑制剂的效力在实验结合和斑块减少试验中得到了进一步证明。这些结果证明了 MD 模拟探测药物结合机制的能力，以及指导设计以前似乎不可成药的靶标抑制剂的能力。

  DOI：

  10.1021/ja204969m

文献信息

• Inhibitors Of The Influenza A Virus M2 Proton Channel
  申请人：DeGrado William F.

  公开号：US20120028957A1

  公开（公告）日：2012-02-02

  Provided are compounds that are capable of modulating the activity of the influenza A virus via interaction with the M2 transmembrane protein. Also provided are methods for treating an influenza A-affected disease state or infection comprising administering a composition comprising one or more compounds that have been identified as being capable of interaction with the M2 protein.

  提供的化合物能够通过与M2跨膜蛋白相互作用来调节流感A病毒的活性。还提供了治疗受流感A影响的疾病状态或感染的方法，包括给予包含已被确认为能够与M2蛋白相互作用的一个或多个化合物的组合物。
• INHIBITORS OF THE INFLUENZA A VIRUS M2 PROTON CHANNEL
  申请人：The Trustees of The University Of Pennsylvania

  公开号：US20140024635A1

  公开（公告）日：2014-01-23

  Provided are compounds that are capable of modulating the activity of the influenza A virus via interaction with the M2 transmembrane protein. Also provided are methods for treating an influenza A-affected disease state or infection comprising administering a composition comprising one or more compounds that have been identified as being capable of interaction with the M2 protein.

  提供的化合物能够通过与M2跨膜蛋白相互作用来调节流感A病毒的活性。还提供了治疗流感A相关疾病或感染的方法，包括给予含有已被确定为能够与M2蛋白相互作用的一个或多个化合物的组合物。
• 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：——
• US8569284B2
  申请人：——

  公开号：US8569284B2

  公开（公告）日：2013-10-29