trans-4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-chlorofuro[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}cyclohexanol | 1326712-16-6

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: trans-4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-chlorofuro[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}cyclohexanol
• CAS: 1326712-16-6
• 化学式: C₂₂H₁₉ClN₆O₂S
• 分子量: 466.951
• InChiKey: IXXBWYJJOYSCNJ-JOCQHMNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.07
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115.88
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  zinc(II) cyanide 、 trans-4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-chlorofuro[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}cyclohexanol 在 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 以12%的产率得到7-amino-2-(benzo[d][1,2,3]thiadiazol-7-yl)-4-(1-((1r,4r)-4-hydroxycyclohexyl)-1H-pyrazol-4-yl)furo[2,3-c]pyridine-3-carbonitrile
  参考文献：
  名称：

  Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: Optimization of kinase selectivity and pharmacokinetics

  摘要：

  The kinase selectivity and pharmacokinetic optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. The intersection of insights from molecular modeling, computational prediction of metabolic sites, and in vitro metabolite identification studies resulted in a simple and unique solution to both of these problems. These efforts culminated in the discovery of compound 13a, a potent, relatively selective inhibitor of TAK1 with good pharmacokinetic properties in mice, which was active in an in vivo model of ovarian cancer. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.054
• 作为产物：
  描述：

  di-tert-butyl (2,3-dichlorofuro[2,3-c]pyridin-7-yl)imidodicarbonate 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 生成 trans-4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)-3-chlorofuro[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}cyclohexanol
  参考文献：
  名称：

  Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: Optimization of kinase selectivity and pharmacokinetics

  摘要：

  The kinase selectivity and pharmacokinetic optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. The intersection of insights from molecular modeling, computational prediction of metabolic sites, and in vitro metabolite identification studies resulted in a simple and unique solution to both of these problems. These efforts culminated in the discovery of compound 13a, a potent, relatively selective inhibitor of TAK1 with good pharmacokinetic properties in mice, which was active in an in vivo model of ovarian cancer. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.054

文献信息

• 7-AMINOFUROPYRIDINE DERIVATIVES
  申请人：Hornberger Keith R.

  公开号：US20120046267A1

  公开（公告）日：2012-02-23

  Compounds of Formula 1, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as tumors driven at least in part by TAK1 or for which an appropriate TAK1 inhibitor is effective. This Abstract is not limiting of the invention.

  公式1的化合物，如下所示并在此定义：其药学上可接受的盐，合成方法，中间体，配方以及使用它们进行疾病治疗的方法，包括治疗癌症，例如由TAK1至少部分驱动的肿瘤或适当的TAK1抑制剂有效的肿瘤。本摘要不限于该发明。
• US8378104B2
  申请人：——

  公开号：US8378104B2

  公开（公告）日：2013-02-19
• [EN] 7-AMINOFUROPYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE LA 7-AMINOFUROPYRIDINE
  申请人：OSI PHARMACEUTICALS LLC

  公开号：WO2011100502A1

  公开（公告）日：2011-08-18

  Compounds of Formula (1), as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as tumors driven at least in part by TAK1 or for which an appropriate TAK1 inhibitor is effective. This Abstract is not limiting of the invention.