Methyl 4-hydroxy-2-methylpyrazolo[1,5-a]pyridine-6-carboxylate | 1415110-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: Methyl 4-hydroxy-2-methylpyrazolo[1,5-a]pyridine-6-carboxylate
• 英文别名: methyl 4-hydroxy-2-methylpyrazolo[1,5-a]pyridine-6-carboxylate
• CAS: 1415110-15-4
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: VZGQMXZWUQGRFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-N,N-dimethylpyrazine-2-carboxamide 、 Methyl 4-hydroxy-2-methylpyrazolo[1,5-a]pyridine-6-carboxylate 在 二甲基氯化铝 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 4-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-2-methyl-N-(5-methylpyrazin-2-yl)pyrazolo[1,5-a]pyridine-6-carboxamide
  参考文献：
  名称：

  The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

  摘要：

  Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.082
• 作为产物：
  描述：

  5-羟基烟酸甲酯 在 盐酸 、 ammonium hydroxide 、 sodium hypochlorite 、 palladium on activated charcoal 、 氢气 、 Methoxytripropylstannan 、 sodium hydride 、 三乙胺 、 三氟乙酸酐 、 sodium hydroxide 、 iron(II) chloride 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醇 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 100.0 ℃ 、206.85 kPa 条件下， 反应 52.67h， 生成 Methyl 4-hydroxy-2-methylpyrazolo[1,5-a]pyridine-6-carboxylate
  参考文献：
  名称：

  The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

  摘要：

  Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.082

文献信息

• The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus
  作者：Jeffrey A. Pfefferkorn、Meihua Tu、Kevin J. Filipski、Angel Guzman-Perez、Jianwei Bian、Gary E. Aspnes、Matthew F. Sammons、Wei Song、Jian-Cheng Li、Christopher S. Jones、Leena Patel、Tim Rasmusson、Dongxiang Zeng、Kapil Karki、Michael Hamilton、Richard Hank、Karen Atkinson、John Litchfield、Robert Aiello、Levenia Baker、Nicole Barucci、Patricia Bourassa、Francis Bourbounais、Theresa D’Aquila、David R. Derksen、Margit MacDougall、Alan Robertson

  DOI：10.1016/j.bmcl.2012.09.082

  日期：2012.12

  Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy. (C) 2012 Elsevier Ltd. All rights reserved.