O-(2-pyridin-2-ylethyl) N-[4-(dimethylamino)phenyl]carbamothioate | 1033590-89-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: O-(2-pyridin-2-ylethyl) N-[4-(dimethylamino)phenyl]carbamothioate
• CAS: 1033590-89-4
• 化学式: C₁₆H₁₉N₃OS
• 分子量: 301.412
• InChiKey: MWNIUUZAFKUMDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-羟乙基吡啶 、 4-二甲氨基苯基硫代异氰酸酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 以28%的产率得到O-(2-pyridin-2-ylethyl) N-[4-(dimethylamino)phenyl]carbamothioate
  参考文献：
  名称：

  Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Parallel synthesis, molecular modelling and structure–activity relationship studies on O-[2-(hetero)arylethyl]-N-phenylthiocarbamates

  摘要：

  In order to expand the structure-activity relationship (SAR) studies on Thiocarbamates (TCs), a recently discovered class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors, 38 analogues of the lead O-[2-(2-pyridyl)ethyl]-N-phenylthiocarbamate 1 were prepared by parallel solution-phase synthesis. The SAR strategy was focused on the variation (mono-and disubstitution) of the N-phenyl ring and the replacement of the 2-pyridyl with 4-pyridyl, 2-thienyl and phenyl rings. The majority of the new TCs proved to prevent the wild-type HIV-1 multiplication in MT-4 cell culture and the most potent congeners displayed an EC50 value of 100 nM. Two TCs were active also at micromolar concentrations against the Y181C- and/or K103N/Y181C-resistant mutants. Docking simulations helped to rationalize the SARs. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.12.050

文献信息

• Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Parallel synthesis, molecular modelling and structure–activity relationship studies on O-[2-(hetero)arylethyl]-N-phenylthiocarbamates
  作者：Sara Cesarini、Andrea Spallarossa、Angelo Ranise、Paola Fossa、Paolo La Colla、Giuseppina Sanna、Gabriella Collu、Roberta Loddo

  DOI：10.1016/j.bmc.2007.12.050

  日期：2008.4.1

  In order to expand the structure-activity relationship (SAR) studies on Thiocarbamates (TCs), a recently discovered class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors, 38 analogues of the lead O-[2-(2-pyridyl)ethyl]-N-phenylthiocarbamate 1 were prepared by parallel solution-phase synthesis. The SAR strategy was focused on the variation (mono-and disubstitution) of the N-phenyl ring and the replacement of the 2-pyridyl with 4-pyridyl, 2-thienyl and phenyl rings. The majority of the new TCs proved to prevent the wild-type HIV-1 multiplication in MT-4 cell culture and the most potent congeners displayed an EC50 value of 100 nM. Two TCs were active also at micromolar concentrations against the Y181C- and/or K103N/Y181C-resistant mutants. Docking simulations helped to rationalize the SARs. (C) 2007 Elsevier Ltd. All rights reserved.