[4-[3-bromo-5-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]-[(1R,2R)-2-[4-(trifluoromethyl)phenyl]cyclopropyl]methanone | 1146354-50-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-[3-bromo-5-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]-[(1R,2R)-2-[4-(trifluoromethyl)phenyl]cyclopropyl]methanone
• CAS: 1146354-50-8
• 化学式: C₂₂H₁₉BrF₆N₂O₃S
• 分子量: 585.365
• InChiKey: XQUHTGGJGBUJIV-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  zinc(II) cyanide 、 [4-[3-bromo-5-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]-[(1R,2R)-2-[4-(trifluoromethyl)phenyl]cyclopropyl]methanone 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 1,1'-bis(diphenylphosphino)ferrocene 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以74%的产率得到3-(trifluoromethyl)-5-[4-[(1R,2R)-2-[4-(trifluoromethyl)phenyl]cyclopropanecarbonyl]piperazin-1-yl]sulfonylbenzonitrile
  参考文献：
  名称：

  1-Sulfonyl-4-acylpiperazines as Selective Cannabinoid-1 Receptor (CB1R) Inverse Agonists for the Treatment of Obesity

  摘要：

  A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford orally bioavailable, highly efficacious, and selective CB1R inverse agonists that caused food intake suppression and body weight reduction in diet-induced obese rats and dogs. It was found that the receptor binding assay predicted in vivo efficacy better than functional antagonist/inverse agonist activities. This observation expedited the structure-activity relationship (SAR) analysis and may have implications beyond the series Of Compounds presented herein.

  DOI：

  10.1021/jm900063x

文献信息

• 1-Sulfonyl-4-acylpiperazines as Selective Cannabinoid-1 Receptor (CB1R) Inverse Agonists for the Treatment of Obesity
  作者：Petr Vachal、Joan M. Fletcher、Tung M. Fong、Cathy C. R.-R. Huang、Julie Lao、Jing C. Xiao、Chun-Pyn Shen、Alison M. Strack、Lauren Shearman、Sloan Stribling、Richard Z. Chen、Andrea Frassetto、Xinchun Tong、Junying Wang、Richard G. Ball、Nancy N. Tsou、Gerard J. Hickey、Donald F. Thompson、Terry D. Faidley、Susan Nicolich、Joana Achanfuo-Yeboah、Donald F. Hora、Jeffrey J. Hale、William K. Hagmann

  DOI：10.1021/jm900063x

  日期：2009.4.23

  A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford orally bioavailable, highly efficacious, and selective CB1R inverse agonists that caused food intake suppression and body weight reduction in diet-induced obese rats and dogs. It was found that the receptor binding assay predicted in vivo efficacy better than functional antagonist/inverse agonist activities. This observation expedited the structure-activity relationship (SAR) analysis and may have implications beyond the series Of Compounds presented herein.