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 | 1449005-22-4

• 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: 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
• CAS: 1449005-22-4
• 化学式: C₂₃H₁₉N₇O₂S
• 分子量: 457.516
• InChiKey: RUNVBUSNWGRNAS-HDJSIYSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  33.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  139.67
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  2,3-dichloro-4-iodofuro[2,3-c]pyridin-7-amine 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 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

文献信息

• Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: Optimization of kinase selectivity and pharmacokinetics
  作者：Keith R. Hornberger、Xin Chen、Andrew P. Crew、Andrew Kleinberg、Lifu Ma、Mark J. Mulvihill、Jing Wang、Victoria L. Wilde、Mark Albertella、Mark Bittner、Andrew Cooke、Salam Kadhim、Jennifer Kahler、Paul Maresca、Earl May、Peter Meyn、Darlene Romashko、Brianna Tokar、Roy Turton

  DOI：10.1016/j.bmcl.2013.06.054

  日期：2013.8

  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.