N-benzyl-1-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)-N-ethylpiperidine-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: N-benzyl-1-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)-N-ethylpiperidine-4-carboxamide
• 英文别名: N-benzyl-1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-N-ethylpiperidine-4-carboxamide
• 化学式: C₂₃H₂₈N₂O₅S
• 分子量: 444.552
• InChiKey: AAJHOEQMTSTUJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(benzyl(ethyl)carbamoyl)piperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 N-benzyl-1-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)-N-ethylpiperidine-4-carboxamide
  参考文献：
  名称：

  Development of a Highly Potent, Novel M₅ Positive Allosteric Modulator (PAM) Demonstrating CNS Exposure: 1-((1H-Indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380)

  摘要：

  A functional high throughput screen identified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylcholine receptor (mAChR) subtype 5 (M-5). Application of rapid analog, iterative parallel synthesis efficiently optimized M-5 potency to arrive at the most potent M-5 PAMs prepared to date and provided tool compound 8n (ML380) demonstrating modest CNS penetration (human M-5 EC50 = 190 nM, rat M-5 EC50 = 610 nM, brain to plasma ratio (K-p) of 0.36).

  DOI：

  10.1021/jm500995y

文献信息

• Development of a Highly Potent, Novel M₅ Positive Allosteric Modulator (PAM) Demonstrating CNS Exposure: 1-((1<i>H</i>-Indazol-5-yl)sulfoneyl)-<i>N</i>-ethyl-<i>N</i>-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380)
  作者：Patrick R. Gentry、Masaya Kokubo、Thomas M. Bridges、Meredith J. Noetzel、Hyekyung P. Cho、Atin Lamsal、Emery Smith、Peter Chase、Peter S. Hodder、Colleen M. Niswender、J. Scott Daniels、P. Jeffrey Conn、Craig W. Lindsley、Michael R. Wood

  DOI：10.1021/jm500995y

  日期：2014.9.25

  A functional high throughput screen identified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylcholine receptor (mAChR) subtype 5 (M-5). Application of rapid analog, iterative parallel synthesis efficiently optimized M-5 potency to arrive at the most potent M-5 PAMs prepared to date and provided tool compound 8n (ML380) demonstrating modest CNS penetration (human M-5 EC50 = 190 nM, rat M-5 EC50 = 610 nM, brain to plasma ratio (K-p) of 0.36).