4-[[3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]-1,4-benzoxazin-3-one | 1359486-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-[[3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]-1,4-benzoxazin-3-one
• CAS: 1359486-87-5
• 化学式: C₁₇H₁₂ClN₃O₃
• 分子量: 341.754
• InChiKey: DKGNVZCCGONMPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氯-N-羟基苯甲脒 在 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 4-[[3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]-1,4-benzoxazin-3-one
  参考文献：
  名称：

  N-Aryl pyrrolidinonyl oxadiazoles as potent mGluR5 positive allosteric modulators

  摘要：

  A novel series of N-aryl pyrrolidinonyl oxadiazoles were identified as mGluR5 positive allosteric modulators (PAMs). Optimization of the initial lead compound 6a led to the identification of the 12c (-) enantiomer as a potent compound with acceptable in vitro clearance, CYP, hERG and PK properties. Para substituted N-aryl pyrrolidinonyl oxadiazoles are mGluR5 PAMs while the meta and ortho substituted N-aryl pyrrolidinonyl oxadiazoles are negative allosteric modulators (NAMs). Para fluoro substitution on the N-aryl group and meta chloro or methyl substituents on the aryl oxadiazole moiety are optimal for mGluR5 PAM efficacy. The existence of an exquisitely sensitive 'PAM to NAM switch' within this chemotype making it challenging for simultaneous optimization of potency and drug-like properties. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.094

文献信息

• N-Aryl pyrrolidinonyl oxadiazoles as potent mGluR5 positive allosteric modulators
  作者：Mathivanan Packiarajan、Christine G. Mazza Ferreira、Sang-Phyo Hong、Andrew D. White、Gamini Chandrasena、Xiaosui Pu、Robbin M. Brodbeck、Albert J. Robichaud

  DOI：10.1016/j.bmcl.2012.06.094

  日期：2012.9

  A novel series of N-aryl pyrrolidinonyl oxadiazoles were identified as mGluR5 positive allosteric modulators (PAMs). Optimization of the initial lead compound 6a led to the identification of the 12c (-) enantiomer as a potent compound with acceptable in vitro clearance, CYP, hERG and PK properties. Para substituted N-aryl pyrrolidinonyl oxadiazoles are mGluR5 PAMs while the meta and ortho substituted N-aryl pyrrolidinonyl oxadiazoles are negative allosteric modulators (NAMs). Para fluoro substitution on the N-aryl group and meta chloro or methyl substituents on the aryl oxadiazole moiety are optimal for mGluR5 PAM efficacy. The existence of an exquisitely sensitive 'PAM to NAM switch' within this chemotype making it challenging for simultaneous optimization of potency and drug-like properties. (C) 2012 Elsevier Ltd. All rights reserved.