3-[(4-propan-2-ylphenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3-[(4-propan-2-ylphenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine
• 化学式: C₁₂H₁₆N₄S
• mdl: MFCD11618268
• 分子量: 248.352
• InChiKey: RUBXAHGZFNPQGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(4-propan-2-ylphenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine 、 乙酰乙酸乙酯 在 溶剂黄146 作用下， 反应 48.0h， 以40.5%的产率得到2-((4-isopropylbenzyl)thio)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one
  参考文献：
  名称：

  Structure based designing of triazolopyrimidone-based reversible inhibitors for kinases involved in NSCLC

  摘要：

  Secondary acquired mutant EGFR (L858R-T790M) overexpressed NSCLC forms one of the prevalent form of resistant NSCLC. Another subset of resistant NSCLC includes amplified cMET in mutant EGFR derived tumours. Thus, in continuation to our previous work on these two major targets of resistant NSCLC, i.e., EGFR (L858R-T790M) and cMET, we are hereby reporting reversible inhibitors of these kinases. Out of 11 lead molecules reported in our previous study, we selected triazolo-pyrimidone (BAS 09867482) scaffold for further development of small molecule dual and reversible inhibitors. Analogues of lead with different substituents on the side ring were sketched and docked in both the target kinases, followed by molecular dynamic simulations. Analogues maintaining hydrophobic interaction with M790 in secondary acquired mutant EGFR (L858R-T790M) were selected and duly synthesized. In vitro biochemical evaluation of these molecules against EGFR (L858R-T790M) and cMET kinase, along with EGFR (L858R) kinase disclosed that three molecules were having significant dual kinase inhibitory potential with IC50, values well below 100 nM. Further, in vitro anti-proliferative assay against three cell lines (A549, A431 and H460) was performed. Out of all, two compounds were having significant potency against these cell lines.

  DOI：

  10.1016/j.bmcl.2019.05.004
• 作为产物：
  描述：

  对异丙基溴苄 、 3-amino-1H-1,2,4-triazole-5-thiol 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以55%的产率得到3-[(4-propan-2-ylphenyl)methylsulfanyl]-1H-1,2,4-triazol-5-amine
  参考文献：
  名称：

  Discovery of Inhibitors of Burkholderia pseudomallei Methionine Aminopeptidase with Antibacterial Activity

  摘要：

  Evaluation of a series of MetAP inhibitors in an in vitro enzyme activity assay led to the first identification of potent molecules that show significant growth inhibition against Burkholderia pseudomallei. Nitroxoline analogues show excellent inhibition potency in the BpMetAP1 enzyme activity assay with the lowest IC50 of 30 nM and inhibit the growth of B. pseudomallei and B. thailandensis at concentrations >= 31 mu M.

  DOI：

  10.1021/ml400034m

文献信息

• Synthesis and fungicidal activity of phenazine-1-carboxylic triazole derivatives
  作者：Xu-Jun Li、Wei Zhang、Chi-Na Zhao、Qing-Lai Wu、Jun-Kai Li、Zhi-Hong Xu

  DOI：10.1080/10286020.2020.1754400

  日期：2021.5.4

  displayed very strong fungicidal activity against one or multiple plant pathogens in vitro and in vivo. Compounds 8b, 8h, and 8i showed a broad spectrum of fungicidal activity. Further field experiments indicated that compounds 8b, 8c, and 8h displayed better efficacy against rice blast (Pyricularia oryzae) than PCA. These data demonstrate that compounds 8b, 8c, and 8h are promising fungicidal candidates, deserving

  摘要 基于天然产物，总共合成了15个新颖的取代的3-（苄基硫烷基）-1H-1,2,4-三唑-5-基胺和10个新颖的取代的3-苄基巯基-1,2,4-三唑衍生物吩嗪-1-羧酸（PCA）。它们的结构通过1 H-NMR，13 C-NMR，HRMS和X射线确认。大多数取代的3-苄基巯基1,2,4-三唑衍生物在体外和体内对一种或多种植物病原体表现出非常强的杀真菌活性。化合物8b，8h和8i表现出广谱的杀真菌活性。进一步的现场实验表明，化合物8b，8c和8h表现出比PCA更好的抗稻瘟病（Pyricularia oryzae）功效。这些数据表明化合物8b，8c和8h是有前途的杀真菌剂候选物，值得进一步研究。
• Discovery of Inhibitors of <i>Burkholderia pseudomallei</i> Methionine Aminopeptidase with Antibacterial Activity
  作者：Phumvadee Wangtrakuldee、Matthew S. Byrd、Cristine G. Campos、Michael W. Henderson、Zheng Zhang、Michael Clare、Ali Masoudi、Peter J. Myler、James R. Horn、Peggy A. Cotter、Timothy J. Hagen

  DOI：10.1021/ml400034m

  日期：2013.8.8

  Evaluation of a series of MetAP inhibitors in an in vitro enzyme activity assay led to the first identification of potent molecules that show significant growth inhibition against Burkholderia pseudomallei. Nitroxoline analogues show excellent inhibition potency in the BpMetAP1 enzyme activity assay with the lowest IC50 of 30 nM and inhibit the growth of B. pseudomallei and B. thailandensis at concentrations >= 31 mu M.
• Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents
  作者：Travis R. Helgren、Congling Chen、Phumvadee Wangtrakuldee、Thomas E. Edwards、Bart L. Staker、Jan Abendroth、Banumathi Sankaran、Nicole A. Housley、Peter J. Myler、Jonathon P. Audia、James R. Horn、Timothy J. Hagen

  DOI：10.1016/j.bmc.2016.11.013

  日期：2017.2

  Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. We tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii. We first identified potent RpMetAP inhibitory species by employing an in vitro enzymatic activity assay. The molecular docking program AutoDock was then utilized to compare published crystal structures of inhibited MetAP species to docked poses of RpMetAP. Based on these in silico and in vitro screens, a subset of 17 compounds was tested for inhibition of R. prowazekii growth in a pulmonary vascular endothelial cell (EC) culture infection model system. All compounds were tested over concentration ranges that were determined to be non-toxic to the ECs and 8 of the 17 compounds displayed substantial inhibition of R. prowazekii growth. These data highlight the therapeutic potential for inhibiting RpMetAP as a novel antimicrobial strategy and set the stage for future studies in pre-clinical animal models of infection. (C) 2016 Elsevier Ltd. All rights reserved.
• Structure based designing of triazolopyrimidone-based reversible inhibitors for kinases involved in NSCLC
  作者：Pankaj Kumar Singh、Dasharath Chaudhari、Sanyog Jain、Om Silakari

  DOI：10.1016/j.bmcl.2019.05.004

  日期：2019.7

  Secondary acquired mutant EGFR (L858R-T790M) overexpressed NSCLC forms one of the prevalent form of resistant NSCLC. Another subset of resistant NSCLC includes amplified cMET in mutant EGFR derived tumours. Thus, in continuation to our previous work on these two major targets of resistant NSCLC, i.e., EGFR (L858R-T790M) and cMET, we are hereby reporting reversible inhibitors of these kinases. Out of 11 lead molecules reported in our previous study, we selected triazolo-pyrimidone (BAS 09867482) scaffold for further development of small molecule dual and reversible inhibitors. Analogues of lead with different substituents on the side ring were sketched and docked in both the target kinases, followed by molecular dynamic simulations. Analogues maintaining hydrophobic interaction with M790 in secondary acquired mutant EGFR (L858R-T790M) were selected and duly synthesized. In vitro biochemical evaluation of these molecules against EGFR (L858R-T790M) and cMET kinase, along with EGFR (L858R) kinase disclosed that three molecules were having significant dual kinase inhibitory potential with IC50, values well below 100 nM. Further, in vitro anti-proliferative assay against three cell lines (A549, A431 and H460) was performed. Out of all, two compounds were having significant potency against these cell lines.