N-(3-{[2-(cyanomethyl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-methylbenzenesulfonamide | 925213-69-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-{[2-(cyanomethyl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-methylbenzenesulfonamide
• 英文别名: N-[3-[2-(cyanomethyl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-methylbenzenesulfonamide
• CAS: 925213-69-0
• 化学式: C₂₃H₂₁N₅O₃S
• 分子量: 447.517
• InChiKey: LBESHTGKYUFINO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-{[2-(cyanomethyl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-methylbenzenesulfonamide 在 盐酸 、 硫酸 、 羟胺 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 49.0h， 生成 4-{6-[(3-aminophenyl)oxy]-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl}-furazan-3-amine
  参考文献：
  名称：

  Discovery of Aminofurazan-azabenzimidazoles as Inhibitors of Rho-Kinase with High Kinase Selectivity and Antihypertensive Activity

  摘要：

  The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.

  DOI：

  10.1021/jm060873p
• 作为产物：
  描述：

  4-羟基-3-硝基吡啶 在 palladium on activated charcoal 叔丁基过氧化氢 、 potassium tert-butylate 、 氢气 、 potassium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 癸烷 、 氨 、 水 、 重水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -35.0~110.0 ℃ 、500.0 kPa 条件下， 反应 60.0h， 生成 N-(3-{[2-(cyanomethyl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  Discovery of Aminofurazan-azabenzimidazoles as Inhibitors of Rho-Kinase with High Kinase Selectivity and Antihypertensive Activity

  摘要：

  The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.

  DOI：

  10.1021/jm060873p

文献信息

• Discovery of Aminofurazan-azabenzimidazoles as Inhibitors of Rho-Kinase with High Kinase Selectivity and Antihypertensive Activity
  作者：Robert A. Stavenger、Haifeng Cui、Sarah E. Dowdell、Robert G. Franz、Dimitri E. Gaitanopoulos、Krista B. Goodman、Mark A. Hilfiker、Robert L. Ivy、Jack D. Leber、Joseph P. Marino,、Hye-Ja Oh、Andrew Q. Viet、Weiwei Xu、Guosen Ye、Daohua Zhang、Yongdong Zhao、Larry J. Jolivette、Martha S. Head、Simon F. Semus、Patricia A. Elkins、Robert B. Kirkpatrick、Edward Dul、Sanjay S. Khandekar、Tracey Yi、David K. Jung、Lois L. Wright、Gary K. Smith、David J. Behm、Christopher P. Doe、Ross Bentley、Zunxuan X. Chen、Erding Hu、Dennis Lee

  DOI：10.1021/jm060873p

  日期：2007.1.1

  The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension.