1-[(4-Methoxyphenyl)methyl]-5-(trifluoromethoxy)spiro[indole-3,3'-oxetane]-2-one | 1432436-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-[(4-Methoxyphenyl)methyl]-5-(trifluoromethoxy)spiro[indole-3,3'-oxetane]-2-one
• CAS: 1432436-63-9
• 化学式: C₁₉H₁₆F₃NO₄
• 分子量: 379.336
• InChiKey: HVZUHCKOYPMYIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,3-Bis(hydroxymethyl)-1-[(4-methoxyphenyl)methyl]-5-(trifluoromethoxy)indol-2-one 在 2,6-二甲基吡啶 、 三氟甲磺酸酐 作用下， 以 二氯甲烷 为溶剂， 以6%的产率得到1-[(4-Methoxyphenyl)methyl]-5-(trifluoromethoxy)spiro[indole-3,3'-oxetane]-2-one
  参考文献：
  名称：

  Discovery of ML326: The first sub-micromolar, selective M5 PAM

  摘要：

  This Letter describes the further chemical optimization of the M-5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M-5 PAMs (M-5 EC50 >10 mu M) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M-5 PAM, ML326 (VU0467903), (human and rat M-5 EC(50)s of 409 nM and 500 nM, respectively) with excellent mAChR selectivity (M-1-M-4 EC(50)s >30 mu M) and a robust 20-fold leftward shift of the ACh CRC. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.032

文献信息

• Discovery of ML326: The first sub-micromolar, selective M5 PAM
  作者：Patrick R. Gentry、Thomas M. Bridges、Atin Lamsal、Paige N. Vinson、Emery Smith、Peter Chase、Peter S. Hodder、Julie L. Engers、Colleen M. Niswender、J. Scott Daniels、P. Jeffrey Conn、Michael R. Wood、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2013.03.032

  日期：2013.5

  This Letter describes the further chemical optimization of the M-5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M-5 PAMs (M-5 EC50 >10 mu M) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M-5 PAM, ML326 (VU0467903), (human and rat M-5 EC(50)s of 409 nM and 500 nM, respectively) with excellent mAChR selectivity (M-1-M-4 EC(50)s >30 mu M) and a robust 20-fold leftward shift of the ACh CRC. (C) 2013 Elsevier Ltd. All rights reserved.