4-methyl-2-m-tolyl-thiazole-5-carbaldehyde | 61292-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-methyl-2-m-tolyl-thiazole-5-carbaldehyde
• 英文别名: 5-Thiazolecarboxaldehyde, 4-methyl-2-(3-methylphenyl)-；4-methyl-2-(3-methylphenyl)-1,3-thiazole-5-carbaldehyde
• CAS: 61292-02-2
• 化学式: C₁₂H₁₁NOS
• mdl: MFCD09694102
• 分子量: 217.291
• InChiKey: BIOHTCQXCRAVLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-methyl-2-m-tolyl-thiazole-5-carbaldehyde 在 potassium carbonate 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-(1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)-4-methyl-2-(m-tolyl)thiazole
  参考文献：
  名称：

  Synthesis and antimycobacterial evaluation of new 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives

  摘要：

  A new series of 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives, 6a-w have been synthesized by click reaction of substituted benzylazide, 5a-d with 5-ethynyl-4-methyl-2-substituted phenylthiazole, 4a-f. The starting compounds 4-ethynyl-2-substituted phenylthiazole (4a-f) were synthesized from the corresponding thiazole aldehyde by using the Ohira-Bestmann reagent. The structure of the synthesized compounds was determined by spectral analysis. All the synthesized compounds were screened for their preliminary antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB, ATCC 25177). Most of the synthesized compounds reported good activity against M. tuberculosis H37Ra strain with IC50 range of 0.58-8.23 mu g/mL. Compounds 6g and 6k reported good antitubercular activity with MIC90 values of 4.71 and 2.22 mu g/mL, respectively. Potential antimycobacterial activity suggested that these compounds could serve as good lead compounds for further optimization and development of a newer antitubercular candidate.[GRAPHICS].

  DOI：

  10.1007/s00044-019-02310-y
• 作为产物：
  描述：

  ethyl 4-methyl-2-(m-tolyl)thiazole-5-carboxylate 在 lithium aluminium tetrahydride 、 2-碘酰基苯甲酸 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 生成 4-methyl-2-m-tolyl-thiazole-5-carbaldehyde
  参考文献：
  名称：

  Synthesis and antimycobacterial evaluation of new 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives

  摘要：

  A new series of 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives, 6a-w have been synthesized by click reaction of substituted benzylazide, 5a-d with 5-ethynyl-4-methyl-2-substituted phenylthiazole, 4a-f. The starting compounds 4-ethynyl-2-substituted phenylthiazole (4a-f) were synthesized from the corresponding thiazole aldehyde by using the Ohira-Bestmann reagent. The structure of the synthesized compounds was determined by spectral analysis. All the synthesized compounds were screened for their preliminary antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB, ATCC 25177). Most of the synthesized compounds reported good activity against M. tuberculosis H37Ra strain with IC50 range of 0.58-8.23 mu g/mL. Compounds 6g and 6k reported good antitubercular activity with MIC90 values of 4.71 and 2.22 mu g/mL, respectively. Potential antimycobacterial activity suggested that these compounds could serve as good lead compounds for further optimization and development of a newer antitubercular candidate.[GRAPHICS].

  DOI：

  10.1007/s00044-019-02310-y

文献信息

• Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells
  作者：Xin Dang、Shuwen Lei、Shuhua Luo、Yixin Hu、Juntao Wang、Dongdong Zhang、Dan Lu、Faqin Jiang、Lei Fu

  DOI：10.1016/j.bioorg.2021.105015

  日期：2021.9

  production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.

  线粒体是细胞维持必要代谢活动的关键能量生产来源。针对功能失调的线粒体特征一直是线粒体相关疾病研究的热点。对癌性线粒体代谢的研究是肿瘤治疗中持续关注的问题。在此，我们基于我们早期对线粒体靶向剂的研究，着手评估新型 TPP-噻唑衍生物家族的抗癌活性。具体而言，我们设计并合成了一系列 TPP-噻唑衍生物，并通过 MTT 测定显示大多数合成的化合物有效抑制了三种癌细胞系（HeLa、PC3 和 MCF-7）。在结构修改后，我们探索了 SAR 关系并确定了最有希望的化合物R13（IC50 of 5.52 μM) 用于进一步研究。同时，我们进行了 ATP 产生测定以评估所选化合物对 HeLa 细胞能量产生的抑制作用。结果显示测试化合物显着抑制癌细胞的ATP产生。总体而言，我们设计并合成了一系列对癌细胞具有显着细胞毒性并有效抑制线粒体能量产生的化合物。
• Synthesis, antimycobacterial screening and molecular docking studies of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives
  作者：Yogita K. Abhale、Abhijit D. Shinde、Keshav K. Deshmukh、Laxman Nawale、Dhiman Sarkar、Prafulla B. Choudhari、Santosh S. Kumbhar、Pravin C. Mhaske

  DOI：10.1007/s00044-017-1988-5

  日期：2017.11

  A series of 4-aryl-4'-methyl-2'-aryl-2,5'-bisthiazole derivatives (5a-o) were synthesized and screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) strains. Five lead compounds (5e, 5f, 5g, 5h, and 5o) were further confirmed from their dose dependent effect against MTB and Bovine-Calmette-Guerin. The most promising compounds 5f (MIC90: 11.32 mu g/mL), 5h (MIC90: 11.59 mu g/mL), and 5o (MIC90: 23.64 mu g/mL) showed strong antitubercular activity against dormant MTB and BCG as well as almost insignificant cytotoxicity up to 100 mu g/mL against HeLa, A549, and PANC-1 human cancer cell lines. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bacteria, Escherichia coli, Pseudomonas flurescence and Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderate activity against fungal strain Candida albicans. Molecular docking studies of these compounds showed significant interactions with crystal structure of the cytochrome P45014 alpha-sterol demethylase (CYP51) PDB ID: 1E9X. Hydrogen bond interactions with SER261 and VAL395 are important interactions for selective inhibition of designed inhibitors. Compounds 5f, 5h, and 5o showed significant interactions with 1E9X. All the experimental results promote us to consider this series as a starting point for the development of novel, selective and more potent antitubercular agents in the future.