2-methyl-3-(butyl)-benzothiazolium bromide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-methyl-3-(butyl)-benzothiazolium bromide
• 英文别名: 3-butyl-2-methylbenzo[d]thiazol-3-ium bromide；3-Butyl-2-methyl-1,3-benzothiazol-3-ium;bromide
• 化学式: Br*C₁₂H₁₆NS
• 分子量: 286.236
• InChiKey: ZCUNCKIJOSGLJV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-3-(butyl)-benzothiazolium bromide 、 4-二苯胺基苯甲醛 、 4-chloro-1,2-dimethylquinolin-1-ium 在 potassium iodide 、 4-甲基哌啶 作用下， 以 正丁醇 为溶剂， 反应 6.0h， 以81.4%的产率得到
  参考文献：
  名称：

  Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer

  摘要：

  人类c-MYC启动子和端粒中的DNA G4结构被认为是重要的药物靶点；然而，开发基于小分子的荧光结合配体，高度选择性地针对这些G4结构而非其他类型的核酸，是具有挑战性的。我们在此报道了一种新的设计小分子的方法，基于非选择性噻唑橙支架，提供与G4基序的侧翼残基和环的双向和多位点相互作用，以获得更好的选择性。这些配体被设计为在G4结合口袋中建立多位点相互作用。这种结构特征可能使分子对c-MYC G4比其他结构具有更高的选择性。利用1H NMR研究的配体-G4相互作用可能表明与末端G四联体的堆积相互作用。此外，与BG4的细胞内共定位研究以及与BRACO-19的细胞竞争实验可能表明，配体在细胞中的结合靶点很可能是G4结构。此外，优先结合于c-MYC启动子或端粒G4的配体能够显著降低MCF-7细胞中c-MYC和hTERT基因的表达，并诱导癌细胞衰老和DNA损伤。该配体在MCF-7肿瘤承载小鼠中的体内抗肿瘤活性也得到了证明。

  DOI：

  10.1093/nar/gkac090
• 作为产物：
  描述：

  2-甲基苯并噻唑 、 1-碘丁烷 反应 24.0h， 以51%的产率得到2-methyl-3-(butyl)-benzothiazolium bromide
  参考文献：
  名称：

  N-Alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles. Potential lead compounds in the fight against Saccharomyces cerevisiae infections

  摘要：

  The synthesis of a variety of N-alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles is reported herein. Their potential as antifungal agents is evaluated by preliminary screening against Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe), and Candida albicans (C albicans). Statistical analyses illustrate a strong relationship between chain length and growth inhibition for S. cerevisiae and S. pombe (p < 0.0001 in every case).Of particular interest is the activity of both sets of compounds against S. cerevisiae, as this is emerging as an opportunistic pathogen, especially in immunosuppressed and immunocompromised patients. Bioassays were set up to compare the efficacy of our range of N-alkylated compounds against classic antifungal agents; Amphotericin B and Thiabendazole. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.031

文献信息

• US4145537A
  申请人：——

  公开号：US4145537A

  公开（公告）日：1979-03-20
• N-Alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles. Potential lead compounds in the fight against Saccharomyces cerevisiae infections
  作者：Andrew R. Tyler、Adeyi Okoh Okoh、Clare L. Lawrence、Vicky C. Jones、Colin Moffatt、Robert B. Smith

  DOI：10.1016/j.ejmech.2013.03.031

  日期：2013.6

  The synthesis of a variety of N-alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles is reported herein. Their potential as antifungal agents is evaluated by preliminary screening against Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe), and Candida albicans (C albicans). Statistical analyses illustrate a strong relationship between chain length and growth inhibition for S. cerevisiae and S. pombe (p < 0.0001 in every case).Of particular interest is the activity of both sets of compounds against S. cerevisiae, as this is emerging as an opportunistic pathogen, especially in immunosuppressed and immunocompromised patients. Bioassays were set up to compare the efficacy of our range of N-alkylated compounds against classic antifungal agents; Amphotericin B and Thiabendazole. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their <i>in vivo</i> antitumor activity against breast cancer
  作者：Wei Long、Bo-Xin Zheng、Ying Li、Xuan-He Huang、Dan-Min Lin、Cui-Cui Chen、Jin-Qiang Hou、Tian-Miao Ou、Wing-Leung Wong、Kun Zhang、Yu-Jing Lu

  DOI：10.1093/nar/gkac090

  日期：2022.2.28

  DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.

  人类c-MYC启动子和端粒中的DNA G4结构被认为是重要的药物靶点；然而，开发基于小分子的荧光结合配体，高度选择性地针对这些G4结构而非其他类型的核酸，是具有挑战性的。我们在此报道了一种新的设计小分子的方法，基于非选择性噻唑橙支架，提供与G4基序的侧翼残基和环的双向和多位点相互作用，以获得更好的选择性。这些配体被设计为在G4结合口袋中建立多位点相互作用。这种结构特征可能使分子对c-MYC G4比其他结构具有更高的选择性。利用1H NMR研究的配体-G4相互作用可能表明与末端G四联体的堆积相互作用。此外，与BG4的细胞内共定位研究以及与BRACO-19的细胞竞争实验可能表明，配体在细胞中的结合靶点很可能是G4结构。此外，优先结合于c-MYC启动子或端粒G4的配体能够显著降低MCF-7细胞中c-MYC和hTERT基因的表达，并诱导癌细胞衰老和DNA损伤。该配体在MCF-7肿瘤承载小鼠中的体内抗肿瘤活性也得到了证明。