5-[2-(4-chlorophenoxy)ethyl]-[1,3,4]thiadiazol-2-ylamine | 842973-73-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[2-(4-chlorophenoxy)ethyl]-[1,3,4]thiadiazol-2-ylamine
• 英文别名: 5-[2-(4-Chloro-phenoxy)-ethyl]-[1,3,4]thiadiazol-2-ylamine；5-[2-(4-chlorophenoxy)ethyl]-1,3,4-thiadiazol-2-amine
• CAS: 842973-73-3
• 化学式: C₁₀H₁₀ClN₃OS
• 分子量: 255.728
• InChiKey: ZUFMTDGRGLKIFZ-UHFFFAOYSA-N

物化性质

• 沸点：
  449.8±51.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  89.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  5-[2-(4-chlorophenoxy)ethyl]-[1,3,4]thiadiazol-2-ylamine 、 2,5-己二酮 在 溶剂黄146 作用下， 反应 1.0h， 以62%的产率得到2-(2-(4-chlorophenoxy)ethyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-1,3,4-thiadiazole
  参考文献：
  名称：

  Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA

  摘要：

  Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.03.001
• 作为产物：
  描述：

  对氯苯酚 在 sodium hydroxide 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 4.5h， 生成 5-[2-(4-chlorophenoxy)ethyl]-[1,3,4]thiadiazol-2-ylamine
  参考文献：
  名称：

  Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA

  摘要：

  Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.03.001

文献信息

• Virtual Screening Identification of Nonfolate Compounds, Including a CNS Drug, as Antiparasitic Agents Inhibiting Pteridine Reductase
  作者：Stefania Ferrari、Federica Morandi、Domantas Motiejunas、Erika Nerini、Stefan Henrich、Rosaria Luciani、Alberto Venturelli、Sandra Lazzari、Samuele Calò、Shreedhara Gupta、Veronique Hannaert、Paul A. M. Michels、Rebecca C. Wade、M. Paola Costi

  DOI：10.1021/jm1010572

  日期：2011.1.13

  Folate analogue inhibitors of Leishmania major pteridine reductase (PTR1) are potential antiparasitic drug candidates for combined therapy with dihydrofolate reductase (DHFR) inhibitors To identify new molecules with specificity for PTR1, we carried out a virtual screening of the Available Chemicals Directory (ACD) database to select compounds that could interact with L major PTR1 but not with human DHFR Through two rounds of drug discovery, we successfully identified eighteen drug-like molecule, with low micromolar affinities and high in vitro specificity profiles Their efficacy against Leishmania species was studied in cultured cells of the promastigote stage, using the compounds both alone and in combination with 1 (pyrimethamine, 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine) Six compounds showed efficacy only in combination In toxicity tests against human fibroblasts, several compounds showed low toxicity One compound, 5c (riluzole, 6-(trifluoromethoxy)-1,3-benzothiazol-2-ylamine,), a known drug approved for CNS pathologies, was active in combination and is suitable for early preclinical evaluation of its potential for label extension as a PTR1 inhibitor and antiparasitic drug candidate