1-(methylamino)isoquinoline-7-carboxylic acid hydrochloride | 1451154-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(methylamino)isoquinoline-7-carboxylic acid hydrochloride
• CAS: 1451154-39-4
• 化学式: C₁₁H₁₀N₂O₂*ClH
• 分子量: 238.674
• InChiKey: CZBKHOFXOPJRDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  62.22
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2′-tert-butyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(2′H)-one hydrochloride 、 1-(methylamino)isoquinoline-7-carboxylic acid hydrochloride 在 4-二甲氨基吡啶 、 1-丙基磷酸酐 、 三乙胺 、 碳酸氢钠 作用下， 以 二氯甲烷 、 乙酸乙酯 、 水 为溶剂， 反应 18.34h， 以40%的产率得到2'-(tert-butyl)-1-(1-(methylamino)isoquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t
• 作为产物：
  描述：

  ethyl 1-(methylamino)isoquinoline-7-carboxylate 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 以72%的产率得到1-(methylamino)isoquinoline-7-carboxylic acid hydrochloride
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t