3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)aniline | 1224172-00-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)aniline
• 英文别名: 3-Methoxy-4-[2-(2-trimethylsilylethoxymethoxy)propoxy]aniline
• CAS: 1224172-00-2
• 化学式: C₁₆H₂₉NO₄Si
• 分子量: 327.496
• InChiKey: CPKMSGNEYURDSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.37
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  62.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-4-(ethoxycarbonyl)-1H-pyrazole-3-carboxylic acid 、 3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)aniline 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 ethyl 1-(4-chlorophenyl)-3-(3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)phenylcarbamoyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup

  摘要：

  Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.008
• 作为产物：
  描述：

  (2-((1-(2-methoxy-4-nitrophenoxy)propan-2-yloxy)methoxy)ethyl)trimethylsilane 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 以99%的产率得到3-methoxy-4-(2-((2-(trimethylsilyl)ethoxy)methoxy)propoxy)aniline
  参考文献：
  名称：

  [EN] AZOLOPYRROLONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
  [FR] ANTAGONISTES DE RÉCEPTEUR-1 DE L'HORMONE DE MÉLANO-CONCENTRATION D'AZOLOPYRROLONE

  摘要：

  公开号：

  WO2010047956A9

文献信息

• [EN] AZOLOPYRROLONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR-1 DE L'HORMONE DE MÉLANO-CONCENTRATION D'AZOLOPYRROLONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010047956A9

  公开（公告）日：2011-10-06
• Dihydropyrrolopyrazol-6-one MCHR1 antagonists for the treatment of obesity: Insights on in vivo efficacy from a novel FLIPR assay setup
  作者：Pratik Devasthale、Wei Wang、Andres S. Hernandez、Fang Moore、Kishore Renduchintala、Radhakrishnan Sridhar、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、Yi-Xin Li、Brian J. Murphy、Jeffrey A. Robl、William N. Washburn

  DOI：10.1016/j.bmcl.2015.05.008

  日期：2015.7

  Our investigation of the structure-activity and structure-liability relationships for dihydropyrrolopyrazol-6-one MCHR1 antagonists revealed that off-rate characteristics, inferred from potencies in a FLIPR assay following a 2 h incubation, can impact in vivo efficacy. The in vitro and exposure profiles of dihydropyrrolopyrazol-6-ones 1b and 1e were comparable to that of the thienopyrimidinone counterparts 41 and 43 except for a much faster MCHR1 apparent off-rate. The greatly diminished dihydropyrrolopyrazol-6-one anti-obesity response may be the consequence of this rapid off-rate. (C) 2015 Elsevier Ltd. All rights reserved.