5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: BBTNJRYVRKDPQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid 、 L-苯甘氨醇 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 以42%的产率得到(S)-N-(2-hydroxy-1-phenylethyl)-5-(4-methoxyphenyl)-1H-indazole-3-carboxamide
  参考文献：
  名称：

  Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy

  摘要：

  Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. Oh the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7). Compound 7 was advanced to first-in-human trial for the treatment of diabetic nephropathy.

  DOI：

  10.1021/acs.jmedchem.6b00866
• 作为产物：
  描述：

  5-溴吲唑-3-甲酸 、 4-甲氧基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 水 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 62.0h， 以62%的产率得到5-(4-methoxyphenyl)-1H-indazole-3-carboxylic acid
  参考文献：
  名称：

  Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy

  摘要：

  Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. Oh the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7). Compound 7 was advanced to first-in-human trial for the treatment of diabetic nephropathy.

  DOI：

  10.1021/acs.jmedchem.6b00866

文献信息

• Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1<i>H</i>-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy
  作者：Kimberly O. Cameron、Daniel W. Kung、Amit S. Kalgutkar、Ravi G. Kurumbail、Russell Miller、Christopher T. Salatto、Jessica Ward、Jane M. Withka、Samit K. Bhattacharya、Markus Boehm、Kris A. Borzilleri、Janice A. Brown、Matthew Calabrese、Nicole L. Caspers、Emily Cokorinos、Edward L. Conn、Matthew S. Dowling、David J. Edmonds、Heather Eng、Dilinie P. Fernando、Richard Frisbie、David Hepworth、James Landro、Yuxia Mao、Francis Rajamohan、Allan R. Reyes、Colin R. Rose、Tim Ryder、Andre Shavnya、Aaron C. Smith、Meihua Tu、Angela C. Wolford、Jun Xiao

  DOI：10.1021/acs.jmedchem.6b00866

  日期：2016.9.8

  Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. Oh the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7). Compound 7 was advanced to first-in-human trial for the treatment of diabetic nephropathy.