ethyl 3-(3-(4-chloro-2,5-dimethoxyphenyl)thioureido)propanoate | 1159074-17-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 3-(3-(4-chloro-2,5-dimethoxyphenyl)thioureido)propanoate
• 英文别名: ethyl 3-[(4-chloro-2,5-dimethoxyphenyl)carbamothioylamino]propanoate
• CAS: 1159074-17-5
• 化学式: C₁₄H₁₉ClN₂O₄S
• 分子量: 346.835
• InChiKey: DANYOQLEYAOVTJ-UHFFFAOYSA-N

物化性质

• 熔点：
  84-85 °C
• 沸点：
  456.5±55.0 °C(predicted)
• 密度：
  1.290±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-2,5-二甲氧基苯胺 以 氯仿 为溶剂， 反应 4.5h， 生成 ethyl 3-(3-(4-chloro-2,5-dimethoxyphenyl)thioureido)propanoate
  参考文献：
  名称：

  Structure–activity relationship studies of 1-(4-chloro-2,5-dimethoxyphenyl)-3-(3-propoxypropyl)thiourea, a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type-1

  摘要：

  The reverse transcriptase (RT) of the human immunodeficiency virus type-1 (HIV-1) is still a prime target for drug development due to the continuing need to block drug-resistant RT mutants by new inhibitors. We have previously identified 1-(4-chloro-2,5-dimethoxyphenyl)-3-(3-propoxypropyl)thiourea, compound 1, as a potent RI inhibitor from an available chemical library. Here, we further modified this compound to study structure activity relationships when replacing various groups in the molecule. Different functional groups were systematically introduced on the aromatic ring and the aliphatic chain of the compound was modified. The effect of these modifications on viral infectivity was then evaluated. The most potent compound found was propyl 4-(amino-N-(4-chloro-2,5-dimethoxyphenyl)methanethioamino)butanoate, 45c, which inhibited infectivity with a calculated IC50 of about 1.1 mu M. Docking studies identified potential important interactions between the top scoring ligands and HIV-1 RT, and the predicted relative affinity of the ligands was found to be in agreement with the experimental results. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.003

文献信息

• [EN] NOVEL REVERSE TRANSCRIPTASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE TRANSCRIPTASE INVERSE
  申请人：UNIV RAMOT

  公开号：WO2009069132A2

  公开（公告）日：2009-06-04

  Compounds that are capable of inhibiting an activity of a reverse transcriptase are disclosed. Further disclosed are pharmaceutical compositions containing these compounds, and methods of inhibiting an activity of reverse transcriptase and/or of a mutant thereof and of treating an infection caused by a retrovirus, utilizing these compounds. The disclosed compounds are either identified by computational means or are designed and newly prepared based on structural features identified, at least in part, by computational means. Thus, further disclosed is a method of identifying candidate compounds for inhibiting an activity of a wild type reverse transcriptase and/or for treating a viral infection caused by a retrovirus.
• Structure–activity relationship studies of 1-(4-chloro-2,5-dimethoxyphenyl)-3-(3-propoxypropyl)thiourea, a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type-1
  作者：Michal Weitman、Keti Lerman、Abraham Nudelman、Dan Thomas Major、Amnon Hizi、Alon Herschhorn

  DOI：10.1016/j.ejmech.2010.11.003

  日期：2011.2

  The reverse transcriptase (RT) of the human immunodeficiency virus type-1 (HIV-1) is still a prime target for drug development due to the continuing need to block drug-resistant RT mutants by new inhibitors. We have previously identified 1-(4-chloro-2,5-dimethoxyphenyl)-3-(3-propoxypropyl)thiourea, compound 1, as a potent RI inhibitor from an available chemical library. Here, we further modified this compound to study structure activity relationships when replacing various groups in the molecule. Different functional groups were systematically introduced on the aromatic ring and the aliphatic chain of the compound was modified. The effect of these modifications on viral infectivity was then evaluated. The most potent compound found was propyl 4-(amino-N-(4-chloro-2,5-dimethoxyphenyl)methanethioamino)butanoate, 45c, which inhibited infectivity with a calculated IC50 of about 1.1 mu M. Docking studies identified potential important interactions between the top scoring ligands and HIV-1 RT, and the predicted relative affinity of the ligands was found to be in agreement with the experimental results. (C) 2010 Elsevier Masson SAS. All rights reserved.