2,2-bis(ethyloxy)ethyl(1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)carbamate | 786700-29-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2,2-bis(ethyloxy)ethyl(1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)carbamate
• 英文别名: 1-(2,2-Diethoxyethyl)-3-[1-[1-(4-methoxy-2-methylphenyl)-6-methyl-2,3-dihydropyrrolo[2,3-b]pyridin-4-yl]pyrazol-3-yl]urea
• CAS: 786700-29-6
• 化学式: C₂₆H₃₄N₆O₄
• 分子量: 494.594
• InChiKey: WSVFQKILPGOQTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,2-bis(ethyloxy)ethyl(1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)carbamate 在 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.75h， 以45%的产率得到1-(1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)-1,3-dihydro-2H-imidazol-2-one
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.

  DOI：

  10.1021/jm800744m
• 作为产物：
  描述：

  phenyl (1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)carbamate 、 氨基乙醛缩二乙醇 在 吡啶 作用下， 反应 3.0h， 以84%的产率得到2,2-bis(ethyloxy)ethyl(1-{6-methyl-1-[2-methyl-4-(methyloxy)phenyl]-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)carbamate
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.

  DOI：

  10.1021/jm800744m