Surineni Goverdhan, Marvadi Sandeep Kumar, Yogeeswari Perumal, Sriram Dharmarajan, Kantevari Srinivas
Department of Crop Protection Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.
Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
Bioorg Med Chem Lett. 2018 May 15;28(9):1610-1614. doi: 10.1016/j.bmcl.2018.03.048. Epub 2018 Mar 19.
Herein described the design, synthesis and antitubercular evaluation of novel series of dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2-aminothiazoles and their cinnamamide analogs. One pot condensation of N-methyl carbazole, dibenzofuran and dibenzothiophene methyl ketones with thiourea in the presence of Iodine and CuO gave respective 2-aminothiazoles 4-6 in very good yields. Aminothiazoles were further coupled with substituted cinnamic acids using acid-amine coupling conditions to give desired cinnamamide analogs 8a-e, 9a-e and 10a-e. All the newly synthesized compounds were fully characterized by their NMR and mass spectral analysis. In vitro screening of new derivatives against Mycobacterium tuberculosis H37Rv (Mtb) resulted 8c, 10d and 10e (MIC: 0.78 µg/mL) and 2-aminothiazoles 5 and 6 (MIC: 1.56 µg/mL) as potent compounds with lower cytotoxicity profile.
本文描述了新型系列二苯并呋喃、二苯并噻吩和N-甲基咔唑连接的2-氨基噻唑及其肉桂酰胺类似物的设计、合成和抗结核评估。在碘和氧化铜存在下，N-甲基咔唑、二苯并呋喃和二苯并噻吩甲基酮与硫脲一锅缩合，以非常好的产率得到相应的2-氨基噻唑4-6。使用酸-胺偶联条件将氨基噻唑与取代的肉桂酸进一步偶联，得到所需的肉桂酰胺类似物8a-e、9a-e和10a-e。所有新合成的化合物均通过核磁共振和质谱分析进行了全面表征。对新衍生物针对结核分枝杆菌H37Rv（Mtb）的体外筛选结果显示，8c、10d和10e（最低抑菌浓度：0.78µg/mL）以及2-氨基噻唑5和6（最低抑菌浓度：1.56µg/mL）是具有较低细胞毒性的有效化合物。
