Pyrazolo[1,5-a]-1,3,5-triazine, 13-18 | 1149605-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Pyrazolo[1,5-a]-1,3,5-triazine, 13-18
• 英文别名: 8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-pentan-2-ylpyrazolo[1,5-a][1,3,5]triazin-4-amine
• CAS: 1149605-21-9
• 化学式: C₁₉H₂₆N₆O
• 分子量: 354.455
• InChiKey: MDAUINVHTWWWPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-chloro-2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl)[1,5-a]pyrazolo-1,3,5-triazine 、 2-氨基戊烷 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 Pyrazolo[1,5-a]-1,3,5-triazine, 13-18
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 8-(Pyrid-3-yl)pyrazolo[1,5-a]-1,3,5-triazines: Potent, Orally Bioavailable Corticotropin Releasing Factor Receptor-1 (CRF₁) Antagonists

  摘要：

  This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. These CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 6.1 +/- 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials.

  DOI：

  10.1021/jm900025h

文献信息

• Synthesis and Structure−Activity Relationships of 8-(Pyrid-3-yl)pyrazolo[1,5-<i>a</i>]-1,3,5-triazines: Potent, Orally Bioavailable Corticotropin Releasing Factor Receptor-1 (CRF₁) Antagonists
  作者：Paul J. Gilligan、Todd Clarke、Liqi He、Snjezana Lelas、Yu-Wen Li、Karen Heman、Lawrence Fitzgerald、Keith Miller、Ge Zhang、Anne Marshall、Carol Krause、John F. McElroy、Kathyrn Ward、Kim Zeller、Harvey Wong、Steven Bai、Joanne Saye、Scott Grossman、Robert Zaczek、Stephen P. Arneric、Paul Hartig、David Robertson、George Trainor

  DOI：10.1021/jm900025h

  日期：2009.5.14

  This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. These CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 6.1 +/- 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials.