4546-25-2Relevant academic research and scientific papers
Metal-free C-H methylation and acetylation of heteroarenes with PEG-400
Kudale, Vishal Suresh,Wang, Jeh-Jeng
, p. 3506 - 3511 (2020/06/25)
The generation of a methyl carbon source from renewable and cheap sources is challenging. Herein, we describe a novel and an efficient route for methylation and acetylation of aza-heteroarenes using PEG-400 under O2and TsOH·H2O for the first time by tuning the reaction conditions using a different set of starting materials. The key features of the current protocol are oxidative C-O and C-C bond scission under metal-free conditions with good functional group tolerance, and a broad substrate scope. The potential applicability of the designed methodology was demonstrated for the synthesis of central nervous system (CNS) depressant and anticonvulsant drug molecules by a one-pot strategy.
Synthesis and evaluation of new quinazolin-4(3H)-one derivatives as potent antibacterial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis
Gatadi, Srikanth,Gour, Jitendra,Shukla, Manjulika,Kaul, Grace,Dasgupta, Arunava,Madhavi,Chopra, Sidharth,Nanduri, Srinivas
, p. 287 - 308 (2019/05/15)
Staphylococcus aureus and Mycobacterium tuberculosis are major causative agents responsible for serious nosocomial and community-acquired infections impacting healthcare systems globally. Over several decades, these pathogens have developed resistance to multiple antibiotics significantly affecting morbidity and mortality. Thus, these recalcitrant pathogens are amongst the most formidable microbial pathogens for which international healthcare agencies have mandated active identification and development of new antibacterial agents for chemotherapeutic intervention. In our present work, a series of new quinazolin-4(3H)-one derivatives were designed, synthesized and evaluated for their antibacterial activity against ESKAP pathogens and pathogenic mycobacteria. The experiments revealed that 4'c, 4'e, 4'f and 4'h displayed selective and potent inhibitory activity against Staphylococcus aureus with MIC values ranging from 0.03-0.25 μg/mL. Furthermore, compounds 4'c and 4'e were found to be benign to Vero cells (CC50 = >5 μg/mL) and displayed promising selectivity index (SI) > 167 and > 83.4 respectively. Additionally, 4'c and 4'e demonstrated equipotent MIC against multiple drug-resistant strains of S. aureus including VRSA, concentration dependent bactericidal activity against S. aureus and synergized with FDA approved drugs. Moreover, compound 4′c exhibited more potent activity in reducing the biofilm and exhibited a PAE of ～2 h at 10X MIC which is comparable to levofloxacin and vancomycin. In vivo efficacy of 4'c in murine neutropenic thigh infection model revealed that 4'c caused a similar reduction in cfu as vancomycin. Gratifyingly, compounds 4d, 4e, 9a, 9b, 14a, 4'e and 4'f also exhibited anti-mycobacterial activity with MIC values in the range of 2-16 μg/mL. In addition, the compounds were found to be less toxic to Vero cells (CC50 = 12.5->100 μg/mL), thus displaying a favourable selectivity index. The interesting results obtained here suggest the potential utilization of these new quinazolin-4(3H)-one derivatives as promising antibacterial agents for treating MDR-Staphylococcal and mycobacterial infections.
Cu-free Sonogashira Type Cross-Coupling of 6-Halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl) Quinazolin-4(3H)-ones as Potential Antimicrobial Agents
Poudapally, Suresh,Gurram, Venkateshwarlu,Garlapati, Ramesh,Tulluri, Chiranjeevi,Addepally, Uma,Vidya,Sharma, Somesh,Sen, Subhabrata,Pottabathini, Narender
, p. 2272 - 2286 (2017/07/24)
C(sp)–C(sp2) bond formation via Sonogashira cross-coupling reactions on 6-halo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-ones with appropriate alkynes was explored. Optimization of reaction conditions with various catalysts, ligands, bases, and solvents was conducted. The combination of PdCl2(MeCN)2 with X-Phos proved to be the best metal–ligand system for this conversion in the presence of triethylamine (Et3N) in tetrahydrofuran at room temperature for iodosubstrates, at 80°C for the bromosubstrates in 8?h, and also for the chlorosubstrates in 16?h. We also demonstrated synthesis of a successful diversity-oriented synthesis library of highly functionalized quinazolinones via Cu-free Sonogashira coupling of diverse aryl halides and azido-alkyne (“click”) ligation reactions with substituted azides. The library exhibited significant antimicrobial activity when screened against several microorganisms.
Convenient synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones: Applications towards the synthesis of drugs
Kumar, Dinesh,Jadhavar, Pradeep S.,Nautiyal, Manesh,Sharma, Himanshu,Meena, Prahlad K.,Adane, Legesse,Pancholia, Sahaj,Chakraborti, Asit K.
, p. 30819 - 30825 (2015/04/22)
Simple, convenient, and green synthetic protocols have been developed for the one pot synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones under catalyst and solvent free conditions. The multicomponent reaction (3-MCR) involving isatoic anhydride, an amine, and orthoester afforded the 2,3-disubstituted quinazolin-4(3H)-ones in excellent yields under classical heating at 120 °C for 5 h or under microwave irradiation at 140°C for 20-30 min. The use of ammonium acetate instead of the amine provides the 2-substituted quinazolin-4(3H)-ones. The reactions are compatible with various substituted isatoic anhydrides, aryl/heteroaryl/alkyl/cycloalkyl amines, and orthoesters. The strategies are extended to the one pot tandem condensation involving isatoic anhydride, an amine, orthoester, and aldehyde to afford highly functionalized (E)-3-aryl/heteroaryl-2-styrylquinazolin/(2-(heteroaryl)vinyl)quinazolin-4(3H)-ones. The applications of the methodologies are demonstrated through the synthesis of various drugs which act on the central nervous system such as methaqualone, mebroqualone, mecloqualone, piriquialone, and diproqualone.
