1-[4-[[2-Tert-butyl-5-(1,3-thiazol-2-ylsulfanyl)benzimidazol-1-yl]methyl]piperidin-1-yl]ethanone | 1067154-00-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1-[4-[[2-Tert-butyl-5-(1,3-thiazol-2-ylsulfanyl)benzimidazol-1-yl]methyl]piperidin-1-yl]ethanone
• CAS: 1067154-00-0
• 化学式: C₂₂H₂₈N₄OS₂
• 分子量: 428.623
• InChiKey: NOHVEXYERPZEMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[4-[[2-Tert-butyl-5-(1,3-thiazol-2-ylsulfanyl)benzimidazol-1-yl]methyl]piperidin-1-yl]ethanone 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 生成 1-[4-[[2-Tert-butyl-5-(1,3-thiazol-2-ylsulfonyl)benzimidazol-1-yl]methyl]piperidin-1-yl]ethanone
  参考文献：
  名称：

  5-Sulfonyl-benzimidazoles as selective CB2 agonists-Part 2

  摘要：

  In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.091
• 作为产物：
  描述：

  Tert-butyl 4-[[2-(2,2-dimethylpropanoylamino)-4-[(4-methoxyphenyl)methylsulfanyl]anilino]methyl]piperidine-1-carboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 溶剂黄146 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 1-[4-[[2-Tert-butyl-5-(1,3-thiazol-2-ylsulfanyl)benzimidazol-1-yl]methyl]piperidin-1-yl]ethanone
  参考文献：
  名称：

  5-Sulfonyl-benzimidazoles as selective CB2 agonists-Part 2

  摘要：

  In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.091

文献信息

• BENZIMIDAZOLE CANNABINOID AGONISTS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2142531B1

  公开（公告）日：2015-07-08
• US8193369B2
  申请人：——

  公开号：US8193369B2

  公开（公告）日：2012-06-05
• 5-Sulfonyl-benzimidazoles as selective CB2 agonists-Part 2
  作者：Harrie J.M. Gijsen、Michel A.J. De Cleyn、Michel Surkyn、Guy R.E. Van Lommen、Bie M.P. Verbist、Marjoleen J.M.A. Nijsen、Theo Meert、Jean Van Wauwe、Jeroen Aerssens

  DOI：10.1016/j.bmcl.2011.10.091

  日期：2012.1

  In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis. (C) 2011 Elsevier Ltd. All rights reserved.