N-(2-(2-phenylthiazol-4-yl)ethyl)azepane-1-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: N-(2-(2-phenylthiazol-4-yl)ethyl)azepane-1-carboxamide
• 英文别名: N-[2-(2-phenyl-1,3-thiazol-4-yl)ethyl]azepane-1-carboxamide
• 化学式: C₁₈H₂₃N₃OS
• 分子量: 329.466
• InChiKey: OPJATRBUYSDTIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  73.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2-苯基-1,3-噻唑-4-基)乙腈 在 盐酸 、 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 水 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 44.5h， 生成 N-(2-(2-phenylthiazol-4-yl)ethyl)azepane-1-carboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AND USE OF SAME
  [FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION

  摘要：

  提供了新型杂环化合物，这些化合物在治疗由锥虫引起的疾病中显示出有效性。特别是，本发明的化合物在治疗HAT和/或Chagas病和/或动物非洲锥虫病（AAT）方面具有用途。

  公开号：

  WO2015172196A1

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND USE OF SAME<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION
  申请人：UNIV MONASH

  公开号：WO2015172196A1

  公开（公告）日：2015-11-19

  Novel heterocyclic compounds are provided which display useful efficacy in the treatment of diseases caused by trypanosomatids. Particularly, the compounds of the invention are useful in the treatment of HAT and/or Chagas disease and/or Animal African trypanosomiasis (AAT).

  提供了新型杂环化合物，这些化合物在治疗由锥虫引起的疾病中显示出有效性。特别是，本发明的化合物在治疗HAT和/或Chagas病和/或动物非洲锥虫病（AAT）方面具有用途。
• Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides
  作者：Stephanie Russell、Raphaël Rahmani、Amy J. Jones、Harriet L. Newson、Kevin Neilde、Ignacio Cotillo、Marzieh Rahmani Khajouei、Lori Ferrins、Sana Qureishi、Nghi Nguyen、Maria S. Martinez-Martinez、Donald F. Weaver、Marcel Kaiser、Jennifer Riley、John Thomas、Manu De Rycker、Kevin D. Read、Gavin R. Flematti、Eileen Ryan、Scott Tanghe、Ana Rodriguez、Susan A. Charman、Albane Kessler、Vicky M. Avery、Jonathan B. Baell、Matthew J. Piggott

  DOI：10.1021/acs.jmedchem.6b00442

  日期：2016.11.10

  The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2-(2-phenylthiazol-4-yl)ethyl)amides, carbamates, and ureas, which rapidly, selectively, and potently kill both species of trypanosome. The mode of action of these compounds is unknown but does not involve CYP51 inhibition. They do, however, exhibit clear structure activity relationships, consistent across both trypanosome species. Favorable physicochemical parameters place the best compounds in CNS drug-like chemical space but, as a class, they exhibit poor metabolic stability. One of the best compounds (64a) cleared all signs of T. cruzi infection in mice when CYP metabolism was inhibited, with sterile cure achieved in one mouse. This family of compounds thus shows significant promise for trypanosomiasis drug discovery.