39091-00-4Relevant articles and documents
Synthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds
Dhumal, Sambhaji T.,Deshmukh, Amarsinh R.,Bhosle, Manisha R.,Khedkar, Vijay M.,Nawale, Laxman U.,Sarkar, Dhiman,Mane, Ramrao A.
, p. 3646 - 3651 (2016)
In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a–o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a–o) in the presence of silica supported POCl3yielded better to excellent yields of the title compounds. All the synthesized compounds (6a–o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3?μg/mL. These compounds have shown low cytotoxicity (CC50: >100?μg/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed.
Synthesis and characterizations of novel thiazolyl-thiadiazole derivatives as telomerase activators
Kayagil, Ismail,Mutlu, Ay?e Gül,Bayhan, ülkü,Yilmaz, Inan?,Demirayak, ?eref
, p. 768 - 779 (2018/06/07)
Pyridine-3/4-thiocarboxamide derivatives were used as starting materials for the synthesis of the target compounds. The pyridine-3/4-thiocarboxamide derivatives were reacted with ethyl 2-chloroacetoacetate in ethanol to give the thiazole derivatives (1, 2). The two ethyl thiazole-carboxylate derivatives (1, 2) thus obtained were treated with sodium hydroxide solution and ethanol and converted to carboxylic acids (3, 4). The carboxylic acid derivatives (3, 4) were reacted with thiosemicarbazide in phosphoroxy trichloride and aminothiadiazole rings (5, 6) were formed. Thus, two thiazolyl-thiadiazole amine derivatives (5, 6) were obtained. These two derivatives (5, 6) were converted into two chloroacetamidothiadiazole derivatives (7, 8) by reaction with chloroacetylchloride over the amino group in the presence of triethylamine in acetone. After all these steps, the starting materials (7, 8) needed to reach the target compounds were obtained. With the two derivatives (7, 8) obtained in this last step, phenol and thiophenol derivatives were reacted in acetone in the presence of potassium carbonate. The target compounds, thiazolyl-thiadiazole derivatives (TDA1?16), are completely unique and their structure has been elucidated by elemental analysis, IR, NMR, and MS spectral data. After all these synthesis steps, telomerase activity studies were performed on the target compounds obtained. For this purpose, a PCR ELISA-based TRAP method was used on the heart of zebrafish. According to the enzyme assay results, derivative TDA8 has shown an increase of telomerase enzyme activity.
Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase
Ronkin, Steven M.,Badia, Michael,Bellon, Steve,Grillot, Anne-Laure,Gross, Christian H.,Grossman, Trudy H.,Mani, Nagraj,Parsons, Jonathan D.,Stamos, Dean,Trudeau, Martin,Wei, Yunyi,Charifson, Paul S.
scheme or table, p. 2828 - 2831 (2010/08/19)
Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphlococcus aureus GyrB.
