N-[(1S,2S)-2-hydroxycyclohexyl]-1-(quinolin-6-ylmethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[(1S,2S)-2-hydroxycyclohexyl]-1-(quinolin-6-ylmethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide
• 英文别名: N-[(1S,2S)-2-hydroxycyclohexyl]-1-(quinolin-6-ylmethyl)pyrrolo[3,2-b]pyridine-3-carboxamide
• 化学式: C₂₄H₂₄N₄O₂
• 分子量: 400.48
• InChiKey: NZABUGASWCRVSP-UNMCSNQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-羟甲基喹啉 、 N-[(1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl]-1H-pyrrolo[3,2-b]pyridine-3-carboxamide 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 116.0h， 以36%的产率得到N-[(1S,2S)-2-hydroxycyclohexyl]-1-(quinolin-6-ylmethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide
  参考文献：
  名称：

  Design and optimization of selective azaindole amide M 1 positive allosteric modulators

  摘要：

  Selective activation of the M-1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M-1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.053