6344-77-0Relevant articles and documents
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.
Conversion of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones to N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones by copper-mediated Pd-catalysed cross-coupling reactions
Kri??iūnien?, Vilija,Matulevi?iūt?, Gita,Paliulis, Osvaldas,Rollin, Patrick,?a?kus, Algirdas
, p. 150 - 163 (2017/03/11)
With the purpose of searching for new heterocyclic building blocks, a new method to access N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones from 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives was developed. The synthetic protocol was based on the copper-mediated palladium-catalysed cross-coupling reactions of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones with (het)arylstannanes or their S-benzylated derivatives with (het)arylboronic acids, using CuBr·Me2S and CuMeSal as promoters, respectively. A similar transformation was applied for the preparation of 2-aryl[1]benzothieno[3,2-d]pyrimidin-4(3H)-ones.
Regioselective sulfonylation and N- to O-sulfonyl migration of quinazolin-4(3H)-ones and analogous thienopyrimidin-4(3H)-ones
Mertens, Matthias D.,Pietsch, Markus,Schnakenburg, Gregor,Guetschow, Michael
, p. 8966 - 8979 (2013/10/08)
The sulfonylation of quinazolin-4(3H)-ones and related tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones with mesyl, tosyl, and p-cyanobenzenesulfonyl chloride was studied. A hydrogen substituent at 2-position directed the sulfonyl group to the N-3 position, while alkylsulfanyl or amino substituents led to sulfonylation of the carbonyl oxygen. The latter effect was attributed to steric influence and the positive mesomeric effect of the 2-substituent. An access to N-sulfonylated 2-substituted regioisomers was established. An unexpected 1,3-sulfonyl migration was observed and further analyzed. This process occurred as an intramolecular N- to O-shift as verified by kinetic and crossover experiments.