299442-99-2Relevant articles and documents
Synthesis, characterization and biological evaluation of thiadiazole amide derivatives as nucleoside triphosphate diphosphohydrolases (NTPDases) inhibitors
Abbas, Sadia,Afzal, Saira,Ashraf, Zaman,Hussain, Dilawar,Iqbal, Jamshed,Langer, Peter,Nadeem, Humaira,Sévigny, Jean
, (2021/11/22)
Importance of extracellular nucleotides is widely understood. These nucleotides act as ligand for P2X and P2Y receptors and modulate a variety of biological functions. However, their extracellular concentration is maintained by a chain of enzymes termed as ecto-nucleotidases. Amongst them, nucleoside triphosphate diphosphohydrolases (NTPDases) is an important enzyme family responsible for the dephosphorylation of these nucleotides. Overexpression of NTPDases leads to many pathological conditions such as cancer and thrombosis. So far, only a few NTPDase inhibitors have been reported. Considering this scarcity of (NTPDase) inhibitors, a number of thiadiazole amide derivatives were synthesized and screened against human (h)-NTPDases. Several compounds showed promising inhibitory activity; compound 5a (IC50 (μM); 0.05 ± 0.008) and 5g (IC50 (μM); 0.04 ± 0.006) appeared to be the most distinguished molecules corresponding to h-NTPDase1 and -2. However, h-NTPDase3 was the least susceptible isozyme and only three compounds (5d, 5e, 5j) strongly inhibited h-NTPDase3. Interestingly, compound 5e was recognized as the most active compound that showed dual inhibition against h-NTPDase3 as well as against h-NTPDase8. For better comprehension of binding mode of these inhibitors, most potent inhibitors were docked with their respective isozyme.
Design, synthesis and anti-bacterial evaluation of novel 1,3,4-thiadiazole derivatives bearing a semicarbazone moiety
Wan, Jinlin,Gan, Yiyuan,Hu, Weinan,Meng, Jiao,Tian, Kun,Li, Xiaoqin,Wu, Shouqun,Xu, Yang,Ouyang, Guiping,Wang, Zhenchao
, p. 443 - 450 (2018/03/12)
Novel 1,3,4-thiadiazole derivatives bearing a semicarbazone moiety were prepared and evaluated for their anti-bacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) by performing a turbidimetre test. The products were structurally characterised by IR, 1H NMR, 13C NMR, 19F NMR and HRMS. Anti-bacterial testing showed that most of the evaluated compounds (6a-6s) exhibited excellent activity (≥74.19%) against Xoo at a concentration of 200?μg/mL, with 50% effective concentration (EC50) values ranging from 12.21 to 67.20?μg/mL, which were superior to the commercial antibacterial agent bismerthiazol (92.23?μg/mL). Among them, compound 2-((2-chloro-1H-indol-3-yl)methylene)-N-(5-((2-chlorobenzyl)thio)-1,3,4-thiadiazol-2-yl)hydrazine-1-carboxamide (6b) demonstrated good inhibitory activity against Xac (89.46% at 200?μg/mL) and Xoo (EC50 = 18.28?μg/mL); compound 2-((2-chloro-1H-indol-3-yl)methylene)-N-(5-((4-methoxybenzyl)thio)-1,3,4-thiadiazol-2-yl)hydrazine-1-carboxamide (6g) displayed excellent activity against Xoo with EC50 value of 12.21?μg/mL.
Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease
Liu, Hailong,Wu, Ruoming,Sun, Yanyan,Ye, Yan,Chen, Jing,Luo, Xiaomin,Shen, Xu,Liu, Hong
, p. 6344 - 6352 (2014/12/11)
Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 μM based on in vitro DENV2 NS2B-NS3pro assays.
