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All total 25 Articles be foundAn efficient synthesis of novel spiro[indole-3,8′-pyrano[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine derivatives via organobase-catalyzed three-component reaction of malononitrile, isatin and heterocyclic-1,3-diones
Hosseini, Saedehsadat,Esmaeili, Abbas Ali,Khojastehnezhad, Amir,Notash, Behrouz
, p. 628 - 644 (2021/07/02)
In this research, firstly, some derivatives of sulfur containing [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one have been synthesized and then they were used for the synthesis of novel derivatives of 6′-amino-2,9′-dioxo-2′-phenyl-9′H-spiro[indoline-3,8′-pyrano[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine]-7′-carbonitriles via a one-pot three-component condensation reaction of 7-hydroxy-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives, malononitrile and isatin compounds in the presence of DABCO as a organocatalyst and under solvent-free conditions. In this report, a new family of spiro-pyrano-thiadiazolo-pyrimidine derivatives have been synthesized in short reaction times (10–60 min) and good to excellent yields (80–96%). The structures of all synthesized products have been confirmed by IR, 1H NMR, 13C NMR and mass spectrometry, and the structure of one selected product was characterized by single-crystal X-ray diffraction studies as well.
Aryl or heteroaryl substituted thiadiazole compound and antibacterial application thereof
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Paragraph 0095-0097; 0129-0130, (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-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.
