1-(6-Methoxy-1,3-benzothiazol-2-yl)-3-(1-phenylpropyl)thiourea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 1-(6-Methoxy-1,3-benzothiazol-2-yl)-3-(1-phenylpropyl)thiourea
• 化学式: C₁₈H₁₉N₃OS₂
• 分子量: 357.5
• InChiKey: QYXJMMWBDWBMIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-6-甲氧基苯并噻唑 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.0h， 生成 1-(6-Methoxy-1,3-benzothiazol-2-yl)-3-(1-phenylpropyl)thiourea
  参考文献：
  名称：

  Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives

  摘要：

  Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV- 1). Molecular modeling studies indicated that because of the asymmetric geometry of the non-nucleoside inhibitors (NNRTI) binding pocket, the 'R' stercoisomers would fit the NNRTI binding pocket of the HIV-1 RT much better than the corresponding 'S' stereoisomers, as reflected by their 10(4)-fold lower K-i values. The 'R' stereoisomers of several PETT derivatives inhibited the recombinant RT in vitro with lower IC50 values than their enantiomers. The active compounds were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMCs). All the 'R' isomers again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strains HTLVIIIB in PBMCs at nanomolar concentrations whereas their enantiomers were less potent. The lead compounds for the respective groups were further tested against A17 (NNRTI-resistant, Y181C mutant RT), and A17Var (NNI-resistant Y181C +/- K103N mutant RT) as well as multidrug resistant viral strains. The results indicated that the lead compounds were several logs more potent than the standard NNRTI drug nevirapine. Structure-activity relationship among the derivatives showed preference of pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of both the stereochemistry as well as regiochemistry. Our data provides experimental evidence that the stereochemistry and the regiochemistry of non-nucleoside inhibitors can profoundly affect their anti-HIV activity. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2004.01.019

文献信息

• Effect of stereo and regiochemistry towards wild and multidrug resistant HIV-1 virus: viral potency of chiral PETT derivatives
  作者：Taracad K. Venkatachalam、Chen Mao、Fatih M. Uckun

  DOI：10.1016/j.bcp.2004.01.019

  日期：2004.5

  Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV- 1). Molecular modeling studies indicated that because of the asymmetric geometry of the non-nucleoside inhibitors (NNRTI) binding pocket, the 'R' stercoisomers would fit the NNRTI binding pocket of the HIV-1 RT much better than the corresponding 'S' stereoisomers, as reflected by their 10(4)-fold lower K-i values. The 'R' stereoisomers of several PETT derivatives inhibited the recombinant RT in vitro with lower IC50 values than their enantiomers. The active compounds were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMCs). All the 'R' isomers again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strains HTLVIIIB in PBMCs at nanomolar concentrations whereas their enantiomers were less potent. The lead compounds for the respective groups were further tested against A17 (NNRTI-resistant, Y181C mutant RT), and A17Var (NNI-resistant Y181C +/- K103N mutant RT) as well as multidrug resistant viral strains. The results indicated that the lead compounds were several logs more potent than the standard NNRTI drug nevirapine. Structure-activity relationship among the derivatives showed preference of pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of both the stereochemistry as well as regiochemistry. Our data provides experimental evidence that the stereochemistry and the regiochemistry of non-nucleoside inhibitors can profoundly affect their anti-HIV activity. (C) 2004 Elsevier Inc. All rights reserved.