3-[4-[(2S)-2-(1,3-benzothiazol-6-ylmethylamino)-3-methylbutan-2-yl]triazol-1-yl]-1-(2,3,5,6-tetrafluorophenoxy)heptan-2-one | 1029431-37-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-[4-[(2S)-2-(1,3-benzothiazol-6-ylmethylamino)-3-methylbutan-2-yl]triazol-1-yl]-1-(2,3,5,6-tetrafluorophenoxy)heptan-2-one
• CAS: 1029431-37-5
• 化学式: C₂₈H₃₁F₄N₅O₂S
• 分子量: 577.646
• InChiKey: NRDAGRURPLJETJ-QVWGJOIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3,5,6-四氟苯酚 在 potassium fluoride 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 3-[4-[(2S)-2-(1,3-benzothiazol-6-ylmethylamino)-3-methylbutan-2-yl]triazol-1-yl]-1-(2,3,5,6-tetrafluorophenoxy)heptan-2-one
  参考文献：
  名称：

  Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas’ disease

  摘要：

  Inhibition of the cysteine protease cruzain from Trypanosoma cruzi has been studied pre-clinically as a new chemotherapeutic approach to treat Chagas' disease. Efficacious effects of vinylsulfone-based cruzain inhibitors in animal models support this therapeutic hypothesis. More recently, substrate-activity screening was used to identify nonpeptidic tetrafluorophenoxymethyl ketone inhibitors of cruzain that showed promising efficacy in animal models. Herein we report efforts to further optimize the in vitro potency and in vivo pharmacokinetic properties of this new class of cruzain inhibitors. Through modifications of the P1, P2 and/or P3 positions, new analogs have been identified with reduced lipophilicity, enhanced potency, and improved oral exposure and bioavailability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.066

文献信息

• Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas’ disease
  作者：R. Jeffrey Neitz、Clifford Bryant、Steven Chen、Jiri Gut、Estefania Hugo Caselli、Servando Ponce、Somenath Chowdhury、Haichao Xu、Michelle R. Arkin、Jonathan A. Ellman、Adam R. Renslo

  DOI：10.1016/j.bmcl.2015.06.066

  日期：2015.11

  Inhibition of the cysteine protease cruzain from Trypanosoma cruzi has been studied pre-clinically as a new chemotherapeutic approach to treat Chagas' disease. Efficacious effects of vinylsulfone-based cruzain inhibitors in animal models support this therapeutic hypothesis. More recently, substrate-activity screening was used to identify nonpeptidic tetrafluorophenoxymethyl ketone inhibitors of cruzain that showed promising efficacy in animal models. Herein we report efforts to further optimize the in vitro potency and in vivo pharmacokinetic properties of this new class of cruzain inhibitors. Through modifications of the P1, P2 and/or P3 positions, new analogs have been identified with reduced lipophilicity, enhanced potency, and improved oral exposure and bioavailability. (C) 2015 Elsevier Ltd. All rights reserved.