1362426-33-2Relevant academic research and scientific papers
2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn)
Jian, Yanlin,Forbes, He Eun,Hulpia, Fabian,Risseeuw, Martijn D. P.,Caljon, Guy,Munier-Lehmann, Hélène,Boshoff, Helena I. M.,Van Calenbergh, Serge
, p. 440 - 457 (2021/01/14)
Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.
An efficient and facile synthesis of inhibitors for hepatitis C viral and anti-SARS agents: 4-aryl-5-cyano-1,6-dihydro-2-thiouracils
Rong, Liangce,Yin, Shan,Xia, Sheng,Tao, Shimin,Shi, Yanhui,Tu, Shujiang
experimental part, p. 983 - 993 (2012/08/07)
One-pot, multicomponent reaction for the synthesis of 4-aryl-5-cyano-1,6- dihydro-2-thiouracils via three-component from aromatic aldehydes, ethyl 2-cyanoacetate and S-benzylisothiourea hydrochloride (methyl carbamimidothioate sulfate) under methanol is d
Novel pyrimidinone derivatives: Synthesis, antitumor and antimicrobial evaluation
Taher, Azza,Helwa, Amira Atef
, p. 521 - 530 (2012/06/01)
Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5- carbonitrile (4a-d), a series of mono- and dialkyl derivatives 5a-j and 6a, b was synthesized. Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a-c which were cyclised to give the triazolopyrimidinones 8a-c and the pyrimidotriazinones 9a-c through the reaction with formic acid and chloroacetyl chloride, respectively. Most of the newly synthesized compounds were evaluated for their in-vitro antitumor activity. Compounds 6a and b displayed promising anticancer activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On the other hand, all compounds prepared were screened for their in-vitro antibacterial and antifungal activities. Compounds 5h and j showed significant activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed moderate inhibitory activity against Candida albicans.
