6-bromo-3-(4-(2-(tert-butyldimethylsilyloxy)-2-cyclopropylethoxy)-3-methoxyphenyl)pyrrolo[1,2-f][1,2,4]triazin-4(3H)-one | 1221420-20-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 英文名称: 6-bromo-3-(4-(2-(tert-butyldimethylsilyloxy)-2-cyclopropylethoxy)-3-methoxyphenyl)pyrrolo[1,2-f][1,2,4]triazin-4(3H)-one
• 英文别名: 6-Bromo-3-[4-[2-[tert-butyl(dimethyl)silyl]oxy-2-cyclopropylethoxy]-3-methoxyphenyl]pyrrolo[2,1-f][1,2,4]triazin-4-one
• CAS: 1221420-20-7
• 化学式: C₂₄H₃₂BrN₃O₄Si
• 分子量: 534.525
• InChiKey: IPYHXFXFPZMPGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.44
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-bromo-3-(4-(2-(tert-butyldimethylsilyloxy)-2-cyclopropylethoxy)-3-methoxyphenyl)pyrrolo[1,2-f][1,2,4]triazin-4(3H)-one 、 4-氯苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四丁基氢氧化铵 、 potassium carbonate 作用下， 以 水 、 甲苯 为溶剂， 以17%的产率得到3-(4-(2-(tert-butyldimethylsilyloxy)-2-cyclopropylethoxy)-3-methoxyphenyl)-6-(4-chlorophenyl)pyrrolo[1,2-f][1,2,4]triazin-4(3H)-one
  参考文献：
  名称：

  Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies

  摘要：

  Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 K-i = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.018
• 作为产物：
  描述：

  1-氨基-4-溴-1H-吡咯-2-羧酸甲酯 在 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 3.5h， 生成 6-bromo-3-(4-(2-(tert-butyldimethylsilyloxy)-2-cyclopropylethoxy)-3-methoxyphenyl)pyrrolo[1,2-f][1,2,4]triazin-4(3H)-one
  参考文献：
  名称：

  Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies

  摘要：

  Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 K-i = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.018

文献信息

• Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies
  作者：Pratik Devasthale、Wei Wang、James Mignone、Kishore Renduchintala、Sridhar Radhakrishnan、Jayanthi Dhanapal、Jagannath Selvaraj、Rajesh Kuppusamy、Mary Ann Pelleymounter、Daniel Longhi、Ning Huang、Neil Flynn、Anthony V. Azzara、Kenneth Rohrbach、James Devenny、Suzanne Rooney、Michael Thomas、Susan Glick、Helen Godonis、Susan Harvey、Mary Jane Cullen、Hongwei Zhang、Christian Caporuscio、Paul Stetsko、Mary Grubb、Christine Huang、Lisa Zhang、Chris Freeden、Brian J. Murphy、Jeffrey A. Robl、William N. Washburn

  DOI：10.1016/j.bmcl.2015.09.018

  日期：2015.10

  Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 K-i = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible. (C) 2015 Elsevier Ltd. All rights reserved.