6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid | 1467058-65-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid
• 英文别名: 6-chloro-5-(2′-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid；6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-1H-indole-3-carboxylic acid
• CAS: 1467058-65-6
• 化学式: C₂₁H₁₄ClNO₃
• 分子量: 363.8
• InChiKey: QZIZUCHLAKADOE-UHFFFAOYSA-N

物化性质

• 沸点：
  653.3±50.0 °C(predicted)
• 密度：
  1.424±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴-6-氯吲哚 在 吡啶 、 甲醇 、 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 83.17h， 生成 6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid
  参考文献：
  名称：

  INDOLE AND INDAZOLE COMPOUNDS THAT ACTIVATE AMPK

  摘要：

  本发明涉及激活5'-腺苷单磷酸活化蛋白激酶（AMPK）的吲哚和吲唑化合物的化学式（I）。该发明还包括含有这些化合物的药物组合物以及治疗或预防通过激活AMPK改善的疾病、症状或疾病的方法。

  公开号：

  US20130267493A1

文献信息

• Indole and indazole compounds that activate AMPK
  申请人：Pfizer Inc.

  公开号：US08889730B2

  公开（公告）日：2014-11-18

  The present invention relates to indole and indazole compounds of Formula (I) that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.

  本发明涉及公式（I）的吲哚和吲唑化合物，其激活5'腺苷酸单磷酸活化蛋白激酶（AMPK）。该发明还包括含有这些化合物的药物组合物以及通过激活AMPK治疗或预防疾病，病况或障碍的方法。
• Indole and Indazole Compounds that Activate AMPK
  申请人：PFIZER INC.

  公开号：US20160016940A1

  公开（公告）日：2016-01-21

  The present invention relates to indole and indazole compounds of Formula (I) that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.

  本发明涉及式（I）的吲哚和吲唑化合物，其激活5′腺苷酸单磷酸激活蛋白激酶（AMPK）。本发明还包括含有这些化合物的药物组合物以及治疗或预防通过激活AMPK改善的疾病、状况或障碍的方法。
• 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.
• INDOLE COMPOUNDS THAT ACTIVATE AMPK
  申请人：Pfizer Inc.

  公开号：EP2970177A1

  公开（公告）日：2016-01-20
• US8889730B2
  申请人：——

  公开号：US8889730B2

  公开（公告）日：2014-11-18