4-苄基-5-甲基-4H-[1,2,4]噻唑-3-硫醇 | 91129-84-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-苄基-5-甲基-4H-[1,2,4]噻唑-3-硫醇
• 中文别名: 4-苄基-5-甲基-4H-1,2,4-三唑-3-硫醇
• 英文名称: 4-benzyl-3-methyl-1,2,4-triazole-5-thione
• 英文别名: 4-benzyl-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione；4-benzyl-5-methyl-2,4-dihydro-[1,2,4]triazole-3-thione；4-Benzyl-5-methyl-4h-[1,2,4]triazole-3-thiol；4-benzyl-3-methyl-1H-1,2,4-triazole-5-thione
• CAS: 91129-84-9
• 化学式: C₁₀H₁₁N₃S
• mdl: MFCD02612745
• 分子量: 205.283
• InChiKey: KPEVOVMFLHPYIS-UHFFFAOYSA-N

物化性质

• 溶解度：
  10.9 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  59.7
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-苄基-5-甲基-4H-[1,2,4]噻唑-3-硫醇 在 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 5.0h， 生成 4-(((4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)thio)methyl)benzoic acid
  参考文献：
  名称：

  Fragment-based drug discovery of triazole inhibitors to block PDEδ-RAS protein-protein interaction

  摘要：

  Although mutated Ras protein is well recognized as an important drug target, direct targeting Ras has proven to be a daunting task. Recent studies demonstrated that Ras protein needs PDE delta to relocate to plasma membrane to execute its signaling transduction function, which provides a new avenue for modulating the Ras protein. To find small molecules antagonizing the interactions between PDE delta and Ras, here we presented a successful application of fragment-based drug discovery of PDE delta inhibitors. Under the guidance of crystal structures, we are able to quickly optimize the initial fragment into highly potent inhibitors, with more than 2000-fold improvement in binding activity, which further adds to the arsenal towards the inhibition of Ras signaling in cancer therapy. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.018
• 作为产物：
  描述：

  4-苄基-3-氨基硫脲 在 吡啶 、 sodium hydroxide 作用下， 以 氯仿 为溶剂， 反应 8.0h， 生成 4-苄基-5-甲基-4H-[1,2,4]噻唑-3-硫醇
  参考文献：
  名称：

  Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors

  摘要：

  A novel sulfanyltriazole was discovered as an HIV-1 non-nucleoside reverse transcriptase inhibitor via HTS using a cell-based assay. Chemical modifications and molecular modeling studies were carried out to establish its SAR and understand its interactions with the enzyme. These modifications led to the identification of sulfanyltriazoles with low nanomolar potency for inhibiting HIV-1 replication and promising activities against selected NNRTI resistant mutants. These novel and potent sulfanyltriazoles could serve as advanced leads for further optimization. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.096

文献信息

• 4-Aralkyl-5-substituted-1,2,4-triazole-5-thiols
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0323737A1

  公开（公告）日：1989-07-12

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are described in which, n is 0 to 5; X¹ to X⁵ are any accessible combination of hydrogen, halogen, C₁₋₆alkyl, C₁₋₆alkoxy, cyano, nitro, SONH₂, SO₂NH₂, SO₂CH₃, SO₂CH₂F, SO₂CHF₂, SO₂CF₃, CF₃, CHO, OH, CH₂OH, CO₂H, or CO₂CpH2p+1 wherein p is 1 to 4; R¹ is phenyl substituted by X¹ to X⁵, C₁₋₄alkyl, C₃₋₆cycloalkyl, or an arylC₁₋₄alkyl group substituted by X¹ to X⁵; R² is hydrogen, C₁₋₄alkyl or (CH₂)m-CO₂R³; m is 0 to 5; and R³ is H or C₁₋₄alkyl. These compounds are dopamine-β-hydroxylase inhibitors. Pharmaceutical compositions are described as are methods of use. Processes for the preparation of these compounds are described.

  描述了式（I）的化合物及其药学上可接受的盐，其中，n为0至5；X¹至X⁵为氢、卤素、C₁₋₆烷基、C₁₋₆烷氧基、氰基、硝基、SONH₂、SO₂NH₂、SO₂CH₃、SO₂CH₂F、SO₂CHF₂、SO₂CF₃、CF₃、CHO、OH、CH₂OH、CO₂H或CO₂CpH2p+1的任意可访问组合，其中p为1至4；R¹为被X¹至X⁵取代的苯基、C₁₋₄烷基、C₃₋₆环烷基或被X¹至X⁵取代的芳基C₁₋₄烷基基团；R²为氢、C₁₋₄烷基或（CH₂）m-CO₂R³；m为0至5；R³为H或C₁₋₄烷基。这些化合物是多巴胺-β-羟基化酶抑制剂。描述了药物组合物以及使用方法。描述了这些化合物的制备过程。
• Discovery of a New Drug-like Series of OGT Inhibitors by Virtual Screening
  作者：Elena M. Loi、Tihomir Tomašič、Cyril Balsollier、Kevin van Eekelen、Matjaž Weiss、Martina Gobec、Matthew G. Alteen、David J. Vocadlo、Roland J. Pieters、Marko Anderluh

  DOI：10.3390/molecules27061996

  日期：——

  of serious human pathologies, such as diabetes and cancer. However, the limited availability of potent and selective inhibitors hinders the validation of this potential therapeutic target. To explore new chemotypes that target the active site of OGT, we performed virtual screening of a large library of commercially available compounds with drug-like properties. We purchased samples of the most promising

  O -GlcNAcylation 是一种重要的翻译后修饰，由酶O -β- N安装-乙酰-d-氨基葡萄糖转移酶（OGT）。调节这种酶对于更好地了解其在严重的人类疾病（如糖尿病和癌症）发展中的作用非常有价值。然而，有效和选择性抑制剂的有限可用性阻碍了对这种潜在治疗靶点的验证。为了探索针对 OGT 活性位点的新化学型，我们对具有药物样特性的大型商用化合物库进行了虚拟筛选。我们购买了最有希望的虚拟命中的样本，并使用酶分析来识别真正的线索。通过生成一个小型衍生物库来探索最佳鉴定的 OGT 抑制剂的构效关系。我们的最佳作品展示了一种新型尿苷模拟支架，并用 IC 抑制了重组酶50值为 7 µM。当前的成功代表了设计和开发一组新的 OGT 抑制剂的绝佳起点，这可能证明对探索 OGT 的生物学有用。
• Searching for novel scaffold of triazole non-nucleoside inhibitors of HIV-1 reverse transcriptase
  作者：Tomasz Frączek、Agata Paneth、Rafał Kamiński、Agnieszka Krakowiak、Piotr Paneth

  DOI：10.3109/14756366.2015.1039531

  日期：——

  Azoles are a promising class of the new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds, many possess the same basic structure of an aryl substituted azole ring linked by a thioglycolamide chain with another aromatic ring. In order to find novel extensions for this basic scaffold, we explored the 5-position substitution pattern of triazole NNRTIs using molecular docking followed by the synthesis of selected compounds. We found that heterocyclic substituents in the 5-position of the triazole ring are detrimental to the inhibitory activity of compounds with four-membered thioglycolamide linker and this substitution seems to be viable only for compounds with shorter two-membered linker. Promising compound, N-(4-carboxy-2-chlorophenyl)-2-((4-benzyl-5-methyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetamide, with potent inhibitory activity and acceptable aqueous solubility has been identified in this study that could serve as lead scaffold for the development of novel water-soluble salts of triazole NNRTIs.
• Triazole derivatives as non-nucleoside inhibitors of HIV-1 reverse transcriptase—Structure–activity relationships and crystallographic analysis
  作者：Thorsten A. Kirschberg、Mini Balakrishnan、Wei Huang、Rebecca Hluhanich、Nilima Kutty、Albert C. Liclican、Damian J. McColl、Neil H. Squires、Eric B. Lansdon

  DOI：10.1016/j.bmcl.2007.11.127

  日期：2008.2

  A series of 3,4,5-trisubstituted 1,2,4-4H triazole derivatives was synthesized and investigated for HIV-1 reverse transcriptase inhibition. An X-ray structure with HIV-1 RT secured the binding mode and allowed the key interactions with the enzyme to be identified.
• Malbec, Frederique; Milcent, Rene; Barbier, Geo, Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 1689 - 1698
  作者：Malbec, Frederique、Milcent, Rene、Barbier, Geo

  DOI：——

  日期：——