2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazin-4(3H)-one | 261966-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazin-4(3H)-one
• 英文别名: 8-(2,4-Dichloro-phenyl)-2,7-dimethyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one；8-(2,4-dichlorophenyl)-2,7-dimethyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one
• CAS: 261966-74-9
• 化学式: C₁₃H₁₀Cl₂N₄O
• 分子量: 309.155
• InChiKey: ZHIHXHNLXZXPMS-UHFFFAOYSA-N

物化性质

• 沸点：
  465.5±55.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazin-4(3H)-one 在 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 23.0h， 生成 [8-(2,4-Dichloro-phenyl)-2,7-dimethyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl]-(1-ethyl-pentyl)-amine
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351
• 作为产物：
  描述：

  5-氨基-4-(2,4-二氯苯基)-3-甲基吡唑 在 sodium ethanolate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 22.0h， 生成 2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazin-4(3H)-one
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351