2-(2,4-Dimethoxy-6-methylphenyl)-3-oxobutanenitrile | 1150233-24-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2,4-Dimethoxy-6-methylphenyl)-3-oxobutanenitrile
• CAS: 1150233-24-1
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: QPYYJCGUMYCXDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,4-Dimethoxy-6-methylphenyl)-3-oxobutanenitrile 在 一水合肼 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 4-(2,4-dimethoxy-6-methylphenyl)-5-methyl-1H-pyrazol-3-amine
  参考文献：
  名称：

  8-(4-Methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazines: Selective and Centrally Active Corticotropin-Releasing Factor Receptor-1 (CRF₁) Antagonists

  摘要：

  This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discovery of analogue 12-3. which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 4.7 +/- 2.0 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 12-3 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 12-3 has been advanced to clinical trials.

  DOI：

  10.1021/jm9000242
• 作为产物：
  描述：

  2,4-Dimethoxy-6-methylbenzylcyanid 、 乙酸乙酯 在 sodium 作用下， 生成 2-(2,4-Dimethoxy-6-methylphenyl)-3-oxobutanenitrile
  参考文献：
  名称：

  8-(4-Methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazines: Selective and Centrally Active Corticotropin-Releasing Factor Receptor-1 (CRF₁) Antagonists

  摘要：

  This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discovery of analogue 12-3. which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 4.7 +/- 2.0 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 12-3 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 12-3 has been advanced to clinical trials.

  DOI：

  10.1021/jm9000242

文献信息

• 8-(4-Methoxyphenyl)pyrazolo[1,5-<i>a</i>]-1,3,5-triazines: Selective and Centrally Active Corticotropin-Releasing Factor Receptor-1 (CRF₁) Antagonists
  作者：Paul J. Gilligan、Liqi He、Todd Clarke、Parcharee Tivitmahaisoon、Snjezana Lelas、Yu-Wen Li、Karen Heman、Lawrence Fitzgerald、Keith Miller、Ge Zhang、Anne Marshall、Carol Krause、John McElroy、Kathyrn Ward、Helen Shen、Harvey Wong、Scott Grossman、Gregory Nemeth、Robert Zaczek、Stephen P. Arneric、Paul Hartig、David W. Robertson、George Trainor

  DOI：10.1021/jm9000242

  日期：2009.5.14

  This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discovery of analogue 12-3. which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 4.7 +/- 2.0 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 12-3 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 12-3 has been advanced to clinical trials.