5-chloro-1-(2-methoxy-1-methoxymethylethyl)-4-[1-methoxymeth-(E)-ylidene]-7-methyl-1,2,3,4-tetrahydro[1,6]naphthyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-chloro-1-(2-methoxy-1-methoxymethylethyl)-4-[1-methoxymeth-(E)-ylidene]-7-methyl-1,2,3,4-tetrahydro[1,6]naphthyridine
• 英文别名: (4E)-5-chloro-1-(1,3-dimethoxypropan-2-yl)-4-(methoxymethylidene)-7-methyl-2,3-dihydro-1,6-naphthyridine
• 化学式: C₁₆H₂₃ClN₂O₃
• 分子量: 326.823
• InChiKey: PZHDXLJGQSIJNY-XYOKQWHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  43.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-1-(2-methoxy-1-methoxymethylethyl)-4-[1-methoxymeth-(E)-ylidene]-7-methyl-1,2,3,4-tetrahydro[1,6]naphthyridine 、 2-氨基-5-氯苯腈 在 对甲苯磺酸一水合物 作用下， 以 环丁砜 为溶剂， 反应 1.0h， 生成 5-Chloro-2-[5-(2-methoxy-1-methoxymethyl-ethyl)-7-methyl-4,5-dihydro-3H-1,5,8-triaza-acenaphthylen-1-yl]-benzonitrile
  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
• 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 、 乙腈 为溶剂， 反应 19.17h， 生成 5-chloro-1-(2-methoxy-1-methoxymethylethyl)-4-[1-methoxymeth-(E)-ylidene]-7-methyl-1,2,3,4-tetrahydro[1,6]naphthyridine
  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

文献信息

• Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core
  作者：Brian Dyck、Dimitri E. Grigoriadis、Raymond S. Gross、Zhiqiang Guo、Mustapha Haddach、Dragan Marinkovic、James R. McCarthy、Manisha Moorjani、Collin F. Regan、John Saunders、Michael K. Schwaebe、Tomas Szabo、John P. Williams、Xiaohu Zhang、Haig Bozigian、Ta Kung Chen

  DOI：10.1021/jm050070m

  日期：2005.6.1

  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.