2-(2,4-Dichloro-phenyl)-4-methyl-6-(1-propyl-butyl)-2,6,7,8-tetrahydro-1,2,3,6-tetraaza-acenaphthylene

• 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-(2,4-Dichloro-phenyl)-4-methyl-6-(1-propyl-butyl)-2,6,7,8-tetrahydro-1,2,3,6-tetraaza-acenaphthylene
• 英文别名: 3-(2,4-dichlorophenyl)-9-heptan-4-yl-6-methyl-2,3,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-1,4,6,8(12)-tetraene
• 化学式: C₂₂H₂₆Cl₂N₄
• 分子量: 417.381
• InChiKey: HJLNASIDHYJLFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4-二氯-6-甲基吡啶-3-甲酸乙酯 在 盐酸 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 36.0h， 生成 2-(2,4-Dichloro-phenyl)-4-methyl-6-(1-propyl-butyl)-2,6,7,8-tetrahydro-1,2,3,6-tetraaza-acenaphthylene
  参考文献：
  名称：

  Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core

  摘要：

  Two new classes of tricyclic-based corticotropin-releasing factor (CRF1) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and 22a, respectively, were discovered that potently bind the recombinant CRF1 receptor (K-i = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC50 = 14, 6.8 nM). These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (V-D = 38, 44 L kg(-1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.

  DOI：

  10.1021/jm050070m