1-(2,3,4-trifluorophenyl)-3-(2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)urea | 1338780-89-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-(2,3,4-trifluorophenyl)-3-(2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)urea
• 英文别名: 1-(2,3,4-Trifluorophenyl)-3-(2,6,6-trimethylnorpinan-3-yl)urea；1-(2,3,4-trifluorophenyl)-3-(2,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl)urea
• CAS: 1338780-89-4
• 化学式: C₁₇H₂₁F₃N₂O
• 分子量: 326.362
• InChiKey: BVLMUEUIQIASQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3,4-三氟苯基异氰酸酯 、 2,6,6-trimethylbicyclo[3.1.1]hept-3-ylamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以99%的产率得到1-(2,3,4-trifluorophenyl)-3-(2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)urea
  参考文献：
  名称：

  The structure–activity relationship of urea derivatives as anti-tuberculosis agents

  摘要：

  The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to antitubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.034

文献信息

• The structure–activity relationship of urea derivatives as anti-tuberculosis agents
  作者：Joshua R. Brown、Elton J. North、Julian G. Hurdle、Christophe Morisseau、Jerrod S. Scarborough、Dianqing Sun、Jana Korduláková、Michael S. Scherman、Victoria Jones、Anna Grzegorzewicz、Rebecca M. Crew、Mary Jackson、Michael R. McNeil、Richard E. Lee

  DOI：10.1016/j.bmc.2011.07.034

  日期：2011.9

  The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to antitubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes. (C) 2011 Elsevier Ltd. All rights reserved.