59565-52-5Relevant academic research and scientific papers
Synthesis, docking, and biological evaluation of thiazolidinone derivatives against hepatitis C virus genotype 4a
Al-Behery, Ahmed S.,Elberembally, Kamel M.,Eldawy, Mohammed A.
, p. 1151 - 1165 (2021/04/05)
Hepatitis C virus (HCV) genotype 4a (GT4a) is prevalent in Egypt. It did not gain the necessary scientific focus despite its high resistance. Since the crystal structure NS5B (RNA-dependent RNA polymerase) of HCV GT4a has not been resolved until now, homology modeling was conducted to build and validate the 3D model of the enzyme. Ligand binding sites including the allosteric thumb II pocket were detected and used in lead optimization. Sixty new 4-thiazolidinone derivatives have been virtually designed and docked into thumb II site of HCV NS5B GT4a using rigid docking approach. Eighteen compounds (7a–r) that show good docking scores were synthesized and tested in vitro against NS5B GT4a. Compounds 7b and 7n showed the best inhibitory activity (IC50 = 0.338 and 0.342 μM, respectively). Compounds 7a, 7b, 7c, 7d, 7k, 7n, 7q, and 7r that have IC50 values less than 2 μM were assessed for cellular anti-HCV GT4a activity using human hepatoma cell line (Huh 7.5). The percentages of viral growth inhibition are between 79.67 and 94.77%. Compound 7b is the most active in the in vitro and cellular assays and could be considered a potential new lead for future anti-HCV studies. [Figure not available: see fulltext.]
Aryl or heteroaryl substituted thiadiazole compound and antibacterial application thereof
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Paragraph 0095-0097; 0114-0115, (2021/01/30)
The invention belongs to the technical field of medicines, and particularly relates to an aryl or heteroaryl substituted thiadiazole compound, a preparation method and application thereof as an antibacterial drug. The compound is represented by formula (1
N-(5-phenyl-1, 3, 4-thiadiazole-2-yl) benzamide compound
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Paragraph 0051; 0057; 0063-0065, (2021/06/09)
The invention belongs to the technical field of medicines, relates to a compound with antitumor activity and a specific chemical structure, and in particular relates to an N-((6, 7-dimethoxyquinoline-4-yl) oxy) methyl)-N-(5-phenyl-1, 3, 4-thiadiazole-2-yl) benzamide compound and a preparation method and an application thereof. The structural general formula of the compound is shown in the specification, wherein an R group is mono-substituted or double-substituted phenyl, fluorophenyl, chlorphenyl, bromophenyl, benzyl, benzyloxy, benzene nitro or trifluoromethyl substituted at 2-position, 3-position or 4-position. Pharmacological studies show that the compound provided by the invention has a relatively remarkable proliferation inhibition effect on HER-2 positive breast cancer cells SK-Br-3, the effect is obviously superior to that of HER-2 negative breast cancer cells MCF-7, the compound can be used for preparing antitumor drugs, and a new way is opened up for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.
N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
Xue, Wenjie,Li, Xueyao,Ma, Guixing,Zhang, Hongmin,Chen, Ya,Kirchmair, Johannes,Xia, Jie,Wu, Song
, (2020/02/04)
Due to the occurrence of antibiotic resistance, bacterial infectious diseases have become a serious threat to public health. To overcome antibiotic resistance, novel antibiotics are urgently needed. N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides are a potential new class of antibacterial agents, as one of its derivatives was identified as an antibacterial agent against S. aureus. However, no potency-directed structural optimization has been performed. In this study, we designed and synthesized 37 derivatives, and evaluated their antibacterial activity against S. aureus ATCC29213, which led to the identification of ten potent antibacterial agents with minimum inhibitory concentration (MIC) values below 1 μg/mL. Next, we performed bacterial growth inhibition assays against a panel of drug-resistant clinical isolates, including methicillin-resistant S. aureus, and cytotoxicity assays with HepG2 and HUVEC cells. One of the tested compounds named 1-ethyl-4-hydroxy-2-oxo-N-(5-(thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-3-carboxamide (g37) showed 2 to 128-times improvement compared with vancomycin in term of antibacterial potency against the tested strains (MICs: 0.25–1 μg/mL vs. 1–64 μg/mL) and an optimal selective toxicity (HepG2/MRSA, 110.6 to 221.2; HUVEC/MRSA, 77.6–155.2). Further, comprehensive evaluation indicated that g37 did not induce resistance development of MRSA over 20 passages, and it has been confirmed as a bactericidal, metabolically stable, orally active antibacterial agent. More importantly, we have identified the S. aureus DNA gyrase B as its potential target and proposed a potential binding mode by molecular docking. Taken together, the present work reports the most potent derivative of this chemical series (g37) and uncovers its potential target, which lays a solid foundation for further lead optimization facilitated by the structure-based drug design technique.
Synthesis and antifungal activities of drimane-amide derivatives from sclareol
Ma, Miaofeng,Feng, Jili,Wang, Dezhi,Chen, Shu-Wei,Xu, Hui
, p. 501 - 509 (2018/12/13)
Aim and Objective: Plant diseases are caused by fungal pathogens lead to severe economic losses in many agriculture crops. And the increasing resistance of many fungi to commonly used antifungal agents necessitates the discovery and development of new fungicides. So this study was focused on synthesizing novel skeleton compounds to effectively control plant diseases. Materials and Methods: A series of drimane-amide derivatives were designed, synthesized by aminolysis reaction of amine with intermediate sclareolide which was prepared from sclareol. The structures of all the synthesized compounds were confirmed using1H NMR,13C NMR, and HR-MS (ESI) spectroscopic data. Their in vitro antifungal activity were preliminarily evaluated by using the mycelium growth rate method against five phytopathogenic fungi: Botrytis cinerea, Glomerella cingulata, Alternaria alternate, Alternaria brassicae, and Fusarium graminearum. Results: 23 target compounds were successfully obtained in yields of 52-95%. Compounds358 A2 and A3 displayed favorable inhibitory potency against B. cinerea, G. cingulata and A. brassicae with IC50 values ranging from 3.18 to 10.48 μg/mL. These two compounds displayed higher fungicidal activity than sclareol against all the tested phytopathogenic fungi, and were more effective than the positive control thiabendazole against A. alternate and A. brassicae. The structure-activity relationship studies of compounds A1-10 indicated that both the position and type of substituent on the phenyl ring had significant effects on antifungal activity. Conclusion: The drimane-amide derivatives A2 and A3 were the most promising derivatives and should be selected as new templates for the potential antifungal agents.
Synthesis and molecular simulation study of furoic peptidomimetic derivatives as potent aminopeptodase N inhibitors
Gao, Min,He, Junhua,Xu, Weidong,Lai, Xiaoping,Liu, Fen,Tu, Guogang
, p. 123 - 127 (2018/03/25)
The aminopeptidase N (APN) plays a critical role in angiogenesis and is over-expressed in tumor cells. In this paper, we report the synthesis and enzyme inhibition assay of furoic peptidomimetic compounds. These new compounds exhibit potent inhibitory ability toward APN with IC50 values lying in the micromolar level. The binding mode of inhibitors in APN active site was explained by a molecular simulation study. These data reveal that ligand coordinating with the catalytic Zn-ion is very important for inhibitory activities.
Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase
akir, Gizem,Kücükgüzel, Ilkay,Guhamazumder, Rupa,Tatar, Esra,Manvar, Dinesh,Basu, Amartya,Patel, Bhargav A.,Zia, Javairia,Talele, Tanaji T.,Kaushik-Basu, Neerja
, p. 10 - 22 (2015/01/30)
In continuation of our efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, we synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29-42, together with their synthetic precursors 22-28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 μM. Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 μM. Molecular docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds.
Discovery of thiadiazole amides as potent, S1P3-sparing agonists of sphingosine-1-phosphate 1 (S1P1) receptor
Xu, Heng,Zhang, Haibo,Luan, Linbo,Xu, Yan,Li, Chengyong,Wang, Yonghui,Han, Fangbin,Yang, Ting,Ren, Feng,Xiang, Jia-Ning,Elliott, John D.,Zhao, Yonggang,Guo, Taylor B.,Lu, Hongtao,Zhang, Wei,Hirst, David,Lindon, Matthew,Lin, Xichen
scheme or table, p. 2456 - 2459 (2012/05/05)
High-throughput screening of GSK compound collection led to the discovery of a novel series of thiadiazole amides as potent and S1P3-sparing sphingosine-1-phosphate 1 (S1P1) receptor agonists. Synthesis, structure and activity relationship, selectivity, and some developability properties are described.
Microwave-assisted synthesis of propesticides 1,3,4-thiadiazole aminophosphonates
Wan, Rong,Wang, Peng,Han, Fen,Wang, Yao,Zhang, Jianqiang
experimental part, p. 864 - 870 (2011/04/22)
A novel and easy synthetic route to diethyl (5-substituted phenyl-1,3,4-thiadiazol-2-ylamino) (substituted phenyl) methylphosphonates has been achieved by the reaction of substituted benzylidene-5-(substituted phenyl)-1,3,4-thiadiazol-2-amines and diethyl phosphite under microwave irradiation. These 1,3,4-thiadiazole aminophosphonates were identified by infrared, 1H NMR, and elemental analyses. The target compounds were obtained in better yields (71-89%) and shorter time (10min) than with conventional heating.
Synthesis of 1,3,4-thiadiazole chrysanthemamide derivatives promoted by phenyldichlorophosphate catalysis
Yu, Peng,Wan, Rong,Wang, Peng,Zhang, Jiang-Qiang,He, Qiu
experimental part, p. 719 - 721 (2011/04/24)
A series of novel pro-pesticides with the activity of both 1,3,4-thiadiazole and chrysanthemic acid were synthesised using phenyldichlorophosphate catalysis. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, 1H NMR and elemental
