ethyl 2-[2-[[(2R)-2-phenylpropyl]carbamothioylamino]thiazol-4-yl]acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-[2-[[(2R)-2-phenylpropyl]carbamothioylamino]thiazol-4-yl]acetate
• 英文别名: ethyl 2-[2-[[(2R)-2-phenylpropyl]carbamothioylamino]-1,3-thiazol-4-yl]acetate
• 化学式: C₁₇H₂₁N₃O₂S₂
• 分子量: 363.505
• InChiKey: QDNGTJBOPZKLTM-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸乙酯 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 ethyl 2-[2-[[(2R)-2-phenylpropyl]carbamothioylamino]thiazol-4-yl]acetate
  参考文献：
  名称：

  Effect of stereochemistry on the anti-HIV activity of chiral thiourea compounds

  摘要：

  Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme (NNRTI) of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the NNRTI binding pocket, the R stereoisomers 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 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 (PBMC). All the R isomers once again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strain HTLVIIIB in peripheral blood mononuclear cells (PBMC) at nanomolar concentrations whereas their enantiomers were substantially less potent. The lead compounds in the respective groups were further tested against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var (YISIC+K103N mutant) and RT MDR (V106N). The results showed that the lead compounds were several logs more potent than the standard NNRTI nevirapine. Structure-activity relationship studies also revealed a preference for the pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of regiochemistry. Our data provides experimental evidence that the stereochemistry as well as regiochemistry of NNRTI can profoundly affect their anti-HIV activity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.050

文献信息

• Effect of stereochemistry on the anti-HIV activity of chiral thiourea compounds
  作者：T.K Venkatachalam、C Mao、Fatih.M Uckun

  DOI：10.1016/j.bmc.2004.04.050

  日期：2004.8.1

  Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme (NNRTI) of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the NNRTI binding pocket, the R stereoisomers 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 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 (PBMC). All the R isomers once again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strain HTLVIIIB in peripheral blood mononuclear cells (PBMC) at nanomolar concentrations whereas their enantiomers were substantially less potent. The lead compounds in the respective groups were further tested against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var (YISIC+K103N mutant) and RT MDR (V106N). The results showed that the lead compounds were several logs more potent than the standard NNRTI nevirapine. Structure-activity relationship studies also revealed a preference for the pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of regiochemistry. Our data provides experimental evidence that the stereochemistry as well as regiochemistry of NNRTI can profoundly affect their anti-HIV activity. (C) 2004 Elsevier Ltd. All rights reserved.