N-(2-aminoethyl)-2,6-dichloro-N-(4-chlorophenyl)benzamide hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-aminoethyl)-2,6-dichloro-N-(4-chlorophenyl)benzamide hydrochloride
• 英文别名: N-(2-aminoethyl)-2,6-dichloro-N-(4-chlorophenyl)benzamide;hydrochloride
• 化学式: C₁₅H₁₃Cl₃N₂O*ClH
• 分子量: 380.101
• InChiKey: YZFKYPWZJLQCKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.67
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对氯苯胺 在 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 N-(2-aminoethyl)-2,6-dichloro-N-(4-chlorophenyl)benzamide hydrochloride
  参考文献：
  名称：

  Discovery of N-(2-aminoethyl)-N-benzyloxyphenyl benzamides: New potent Trypanosoma brucei inhibitors

  摘要：

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (HAT), led to the identification of N-(2-aminoethyl)-N-phenyl benzamides as a starting point for hit-to-lead medicinal chemistry. Eighty two analogues were prepared, which led to the identification of a set of highly potent N-(2-aminoethyl)-N-benzyloxyphenyl benzamides with the most potent compound 73 having an in vitro EC50 = 0.001 mu M. The compounds displayed drug like properties when tested in a number of in vitro assays. Compound 73 was orally bioavailable and displayed good plasma and brain exposure in mice, cured 2 out of 3 mice infected with Trypanosoma brucei in acute model when dosed orally at 50 mg/kg once per day for 4 days. Given its potent antiparasitic properties and its ease of synthesis, compound 73 represents a potential lead for the development of drug to treat Human African Trypanosomiasis. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.11.019

文献信息

• Discovery of N-(2-aminoethyl)-N-benzyloxyphenyl benzamides: New potent Trypanosoma brucei inhibitors
  作者：Andriy Buchynskyy、J. Robert Gillespie、Matthew A. Hulverson、Joshua McQueen、Sharon A. Creason、Ranae M. Ranade、Nicole A. Duster、Michael H. Gelb、Frederick S. Buckner

  DOI：10.1016/j.bmc.2016.11.019

  日期：2017.3

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (HAT), led to the identification of N-(2-aminoethyl)-N-phenyl benzamides as a starting point for hit-to-lead medicinal chemistry. Eighty two analogues were prepared, which led to the identification of a set of highly potent N-(2-aminoethyl)-N-benzyloxyphenyl benzamides with the most potent compound 73 having an in vitro EC50 = 0.001 mu M. The compounds displayed drug like properties when tested in a number of in vitro assays. Compound 73 was orally bioavailable and displayed good plasma and brain exposure in mice, cured 2 out of 3 mice infected with Trypanosoma brucei in acute model when dosed orally at 50 mg/kg once per day for 4 days. Given its potent antiparasitic properties and its ease of synthesis, compound 73 represents a potential lead for the development of drug to treat Human African Trypanosomiasis. (C) 2016 Elsevier Ltd. All rights reserved.