6-(5-Fluoro-4-methylpyridin-2-yl)-2-(phenoxymethyl)imidazo[1,2-c]pyrimidin-5-one | 1400633-68-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-(5-Fluoro-4-methylpyridin-2-yl)-2-(phenoxymethyl)imidazo[1,2-c]pyrimidin-5-one
• CAS: 1400633-68-2
• 化学式: C₁₉H₁₅FN₄O₂
• 分子量: 350.352
• InChiKey: WKKSAZHJWFXYRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(5-Fluoro-4-methylpyridin-2-yl)-2-(phenoxymethyl)imidazo[1,2-c]pyrimidin-5-one 在 氢气 作用下， 生成 6-(5-Fluoro-4-methylpyridin-2-yl)-2-(phenoxymethyl)-7,8-dihydroimidazo[1,2-c]pyrimidin-5-one
  参考文献：
  名称：

  Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)

  摘要：

  We report the discovery and SAR of two novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs). Exploration of several structural features in the western and eastern part of the imidazopyrimidinone core and combinations thereof, revealed compound 4a as a mGlu(5) PAM with good in vitro potency and efficacy, acceptable drug metabolism and pharmacokinetic (DMPK) properties and in vivo efficacy in an amphetamine-based model of psychosis. However, the presence of CNS-mediated adverse effects in preclinical species precluded any further in vivo evaluation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.038
• 作为产物：
  描述：

  7-chloro-2-chloromethyl-5-methylsulfanylimidazo[1,2-c]pyrimidine 在 copper(l) iodide 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium carbonate 、 三乙胺 、 lithium hydroxide 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 50.0~120.0 ℃ 、310.27 kPa 条件下， 反应 54.0h， 生成 6-(5-Fluoro-4-methylpyridin-2-yl)-2-(phenoxymethyl)imidazo[1,2-c]pyrimidin-5-one
  参考文献：
  名称：

  Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)

  摘要：

  We report the discovery and SAR of two novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs). Exploration of several structural features in the western and eastern part of the imidazopyrimidinone core and combinations thereof, revealed compound 4a as a mGlu(5) PAM with good in vitro potency and efficacy, acceptable drug metabolism and pharmacokinetic (DMPK) properties and in vivo efficacy in an amphetamine-based model of psychosis. However, the presence of CNS-mediated adverse effects in preclinical species precluded any further in vivo evaluation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.038

文献信息

• SUBSTITUTED IMIDAZOPYRIMIDIN-5(6H)-ONES AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
  申请人：Conn P. Jeffrey

  公开号：US20130245043A1

  公开（公告）日：2013-09-19

  In one aspect, the invention relates to imidazopyrimidin-5(6H)-one analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及咪唑吡嘧啶-5(6H)-酮类似物、其衍生物和相关化合物，这些化合物可作为代谢型谷氨酸受体亚型5（mGluR5）的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神障碍的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意在限制本发明。
• US8865725B2
  申请人：——

  公开号：US8865725B2

  公开（公告）日：2014-10-21
• [EN] SUBSTITUTED IMADAZAPYRINIDIN-5(6H)-ONES AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS<br/>[FR] IMADAZAPYRINIDIN-5(6H)-ONES SUBSTITUÉES EN TANT QUE MODULATEURS ALLOSTÉRIQUES DES RÉCEPTEURS MGLUR5
  申请人：UNIV VANDERBILT

  公开号：WO2012125732A1

  公开（公告）日：2012-09-20

  In one aspect, the invention relates to imidazopyrimidin-5(6H)-one analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)
  作者：María Luz Martín-Martín、José Manuel Bartolomé-Nebreda、Susana Conde-Ceide、Sergio A. Alonso de Diego、Silvia López、Carlos M. Martínez-Viturro、Han Min Tong、Hilde Lavreysen、Gregor J. Macdonald、Thomas Steckler、Claire Mackie、Thomas M. Bridges、J. Scott Daniels、Colleen M. Niswender、Meredith J. Noetzel、Carrie K. Jones、P. Jeffrey Conn、Craig W. Lindsley、Shaun R. Stauffer

  DOI：10.1016/j.bmcl.2015.01.038

  日期：2015.3

  We report the discovery and SAR of two novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs). Exploration of several structural features in the western and eastern part of the imidazopyrimidinone core and combinations thereof, revealed compound 4a as a mGlu(5) PAM with good in vitro potency and efficacy, acceptable drug metabolism and pharmacokinetic (DMPK) properties and in vivo efficacy in an amphetamine-based model of psychosis. However, the presence of CNS-mediated adverse effects in preclinical species precluded any further in vivo evaluation. (C) 2015 Elsevier Ltd. All rights reserved.