N-[4-[2-[[3-sulfamoyl-5-(trifluoromethyl)phenyl]methylamino]-4-(2,2,2-trifluoroethylamino)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-1-(trifluoromethyl)cyclopropane-1-carboxamide | 1318780-07-2

• 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: N-[4-[2-[[3-sulfamoyl-5-(trifluoromethyl)phenyl]methylamino]-4-(2,2,2-trifluoroethylamino)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-1-(trifluoromethyl)cyclopropane-1-carboxamide
• CAS: 1318780-07-2
• 化学式: C₂₈H₂₂F₉N₇O₃S
• 分子量: 707.579
• InChiKey: TZCPEYHVSDZCOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  2,6-dichloro-N-(2,2,2-trifluoroethyl)pyrido[3,2-d]pyrimidin-4-amine 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 水 为溶剂， 反应 11.5h， 生成 N-[4-[2-[[3-sulfamoyl-5-(trifluoromethyl)phenyl]methylamino]-4-(2,2,2-trifluoroethylamino)pyrido[3,2-d]pyrimidin-6-yl]phenyl]-1-(trifluoromethyl)cyclopropane-1-carboxamide
  参考文献：
  名称：

  Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors

  摘要：

  A novel series of HCV replication inhibitors based on a pyrido[3,2-d]primidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).

  DOI：

  10.1021/ml200163b

文献信息

• Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors
  作者：Scott E. Lazerwith、Gina Bahador、Eda Canales、Guofeng Cheng、Lee Chong、Michael O. Clarke、Edward Doerffler、Eugene J. Eisenberg、Jaclyn Hayes、Bing Lu、Qi Liu、Mike Matles、Michael Mertzman、Michael L. Mitchell、Philip Morganelli、Bernard P. Murray、Margaret Robinson、Robert G. Strickley、Megan Tessler、Neeraj Tirunagari、Jianhong Wang、Yujin Wang、Jennifer R. Zhang、Xubin Zheng、Weidong Zhong、William J. Watkins

  DOI：10.1021/ml200163b

  日期：2011.10.13

  A novel series of HCV replication inhibitors based on a pyrido[3,2-d]primidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).