4-{[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy}-2-methyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide | 1245217-01-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-{[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy}-2-methyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide
• 英文别名: 4-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-2-methyl-N-(5-methylpyrazin-2-yl)indazole-6-carboxamide
• CAS: 1245217-01-9
• 化学式: C₂₁H₂₀N₈O₃
• 分子量: 432.442
• InChiKey: CXVAKQOAJSWZLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氯吡嗪-2-甲酰氯 在 盐酸 、 copper(l) iodide 、 二甲基氯化铝 、 caesium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 4-{[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy}-2-methyl-N-(5-methylpyrazin-2-yl)-2H-indazole-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

文献信息

• [EN] SUBSTITUTED INDAZOLE AMIDES AND THEIR USE AS GLUCOKINASE ACTIVATORS<br/>[FR] INDAZOLE AMIDES SUBSTITUÉS
  申请人：PFIZER

  公开号：WO2010103438A1

  公开（公告）日：2010-09-16

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R4, R6, X, Y and Z are as defined herein. The compounds of Formula (I) have been found to act as glucokinase activators. Consequently, the compounds of Formula (I) and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucokinase.

  本发明提供了一种公式(I)化合物或其药用可接受盐，其中R1、R4、R6、X、Y和Z按本文定义。已发现公式(I)的化合物作为葡萄糖激酶激活剂。因此，公式(I)的化合物及其药物组合物可用于治疗由葡萄糖激酶介导的疾病、障碍或状况。
• Substituted Indazole Amides And Their Use As Glucokinase Activators
  申请人：Corbett Jeffrey W.

  公开号：US20110319379A1

  公开（公告）日：2011-12-29

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R 1 , R 4 , R 6 , X, Y and Z are as defined herein. The compounds of Formula (I) have been found to act as glucokinase activators. Consequently, the compounds of Formula (I) and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucokinase.

  本发明提供公式（I）的化合物或其药学上可接受的盐，其中R1、R4、R6、X、Y和Z的定义如本文所述。已经发现公式（I）的化合物可以作为葡萄糖激酶激活剂。因此，公式（I）的化合物及其制备的药物组合物可用于治疗由葡萄糖激酶介导的疾病、紊乱或情况。
• SUBSTITUTED INDAZOLE AMIDES AND THEIR USE AS GLUCOKINASE ACTIVATORS
  申请人：Pfizer Inc.

  公开号：EP2406230A1

  公开（公告）日：2012-01-18
• 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.