N-Butyl-cyclooctanonimin | 13363-14-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-Butyl-cyclooctanonimin
• 英文别名: N-Butylcyclooctanimine；N-butylcyclooctanimine
• CAS: 13363-14-9
• 化学式: C₁₂H₂₃N
• 分子量: 181.321
• InChiKey: MDNRMXGNUMHTAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-Butyl-cyclooctanonimin 在 氯化亚砜 、 水 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 二乙二醇二甲醚 、 甲苯 为溶剂， 反应 5.5h， 生成 1-butyl-N-(1-methylpiperidin-4-yl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxamide
  参考文献：
  名称：

  Selective CB2 agonists with anti-pruritic activity: Discovery of potent and orally available bicyclic 2-pyridones

  摘要：

  The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.030
• 作为产物：
  描述：

  环辛酮 、 正丁胺 以 甲苯 为溶剂， 生成 N-Butyl-cyclooctanonimin
  参考文献：
  名称：

  S-777469的发现：口服CB2激动剂作为止痒药

  摘要：

  据报道，通过调节1-，5-和6-位侧链的大小，发现了基于3-氨基甲酰基-2-吡啶酮衍生物的新型CB2配体。该模板周围的结构-活性关系导致鉴定出S-777469为选择性CB2受体激动剂，该化合物在1.0 mg / kg po和10 mg / kg po下表现出对化合物48/80诱导的刮擦的显着抑制作用（55 ％和61％）。

  DOI：

  10.1016/j.bmcl.2012.02.072

文献信息

• Discovery of S-777469: An orally available CB2 agonist as an antipruritic agent
  作者：Masahide Odan、Natsuki Ishizuka、Yoshiharu Hiramatsu、Masanao Inagaki、Hiroshi Hashizume、Yasuhiko Fujii、Susumu Mitsumori、Yasuhide Morioka、Masahiko Soga、Masashi Deguchi、Kiyoshi Yasui、Akinori Arimura

  DOI：10.1016/j.bmcl.2012.02.072

  日期：2012.4

  The discovery of novel CB2 ligands based on the 3-carbamoyl-2-pyridone derivatives by adjusting the size of side chain at 1-, 5- and 6-position is reported. The structure–activity relationship around this template lead to the identification of S-777469 as a selective CB2 receptor agonist, which exhibited the significant inhibition of scratching induced by Compound 48/80 at 1.0 mg/kg po and 10 mg/kg

  据报道，通过调节1-，5-和6-位侧链的大小，发现了基于3-氨基甲酰基-2-吡啶酮衍生物的新型CB2配体。该模板周围的结构-活性关系导致鉴定出S-777469为选择性CB2受体激动剂，该化合物在1.0 mg / kg po和10 mg / kg po下表现出对化合物48/80诱导的刮擦的显着抑制作用（55 ％和61％）。
• Selective CB2 agonists with anti-pruritic activity: Discovery of potent and orally available bicyclic 2-pyridones
  作者：Ken-ichi Kusakabe、Yasuyoshi Iso、Yukio Tada、Masahiro Sakagami、Yasuhide Morioka、Nobuo Chomei、Satomi Shinonome、Keiko Kawamoto、Hideyuki Takenaka、Kiyoshi Yasui、Hiroshi Hamana、Kohji Hanasaki

  DOI：10.1016/j.bmc.2013.03.030

  日期：2013.6

  The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1. (C) 2013 Published by Elsevier Ltd.