85741-74-8Relevant articles and documents
Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as bacterial topoisomerase IA inhibitors
Yu, Xufen,Zhang, Mingming,Annamalai, Thirunavukkarasu,Bansod, Priyanka,Narula, Gagandeep,Tse-Dinh, Yuk-Ching,Sun, Dianqing
, p. 515 - 527 (2017)
New antibacterial agents with novel target and mechanism of action are urgently needed to combat problematic bacterial infections and mounting antibiotic resistances. Topoisomerase IA represents an attractive and underexplored antibacterial target, as such, there is a growing interest in developing selective and potent topoisomerase I inhibitors for antibacterial therapy. Based on our initial biological screening, fluoroquinophenoxazine 1 was discovered as a low micromolar inhibitor against E.?coli topoisomerase IA. In the literature, fluoroquinophenoxazine analogs have been investigated as antibacterial and anticancer agents, however, their topoisomerase I inhibition was relatively underexplored and there is little structure-activity relationship (SAR) available. The good topoisomerase I inhibitory activity of 1 and the lack of SAR prompted us to design and synthesize a series of fluoroquinophenoxazine analogs to systematically evaluate the SAR and to probe the structural elements of the fluoroquinophenoxazine core toward topoisomerase I enzyme target recognition. In this study, a series of fluoroquinophenoxazine analogs was designed, synthesized, and evaluated as topoisomerase I inhibitors and antibacterial agents. Target-based assays revealed that the fluoroquinophenoxazine derivatives with 9-NH2and/or 6-substituted amine functionalities generally exhibited good to excellent inhibitory activities against topoisomerase I with IC50s ranging from 0.24 to 3.9?μM. Notably, 11a bearing the 6-methylpiperazinyl and 9-amino motifs was identified as one of the most potent topoisomerase I inhibitors (IC50?=?0.48?μM), and showed broad spectrum antibacterial activity (MICs?=?0.78–7.6?μM) against all the bacteria strains tested. Compound 11g with the 6-bipiperidinyl lipophilic side chain exhibited the most potent antituberculosis activity (MIC?=?2.5?μM, SI?=?9.8). In addition, CoMFA analysis was performed to investigate the 3D-QSAR of this class of fluoroquinophenoxazine derivatives. The constructed CoMFA model produced reasonable statistics (q2?=?0.688 and r2?=?0.806). The predictive power of the developed model was obtained using a test set of 7 compounds, giving a predictive correlation coefficient r2predof 0.767. Collectively, these promising data demonstrated that fluoroquinophenoxazine derivatives have the potential to be developed as a new chemotype of potent topoisomerase IA inhibitors with antibacterial therapeutic potential.
An efficient synthesis of ofloxacin and levofloxacin from 3,4- difluoroaniline
Adrio, Javier,Carretero, Juan C.,Garcia Ruano, Jose L.,Pallares, Antonio,Vicioso, Mercedes
, p. 1563 - 1572 (2007/10/03)
The functionalization at either C-2 or C-3 of N-(tert-butoxycarbonyl)- 3,4-difluoroaniline based on its ortho-deprotonation under different experimental conditions is described. This kind of products can be readily applied to the synthesis of ofloxacin, levofloxacin and related compounds.
SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME 3-OXO-3H-PYRIDOPHENOXAZINE-2-CARBOXYLIC ACIDS
Radl, Stanislav,Zikan, Viktor
, p. 506 - 515 (2007/10/02)
Reaction of ethyl 1,4-dihydro-8-hydroxy-4-oxo-3-quinolinecarboxylates XIIIa - XIIIc with 2,4-dinitrochlorobenzene in N,N-dimethylformamide in the presence of sodium hydrogen carbonate yields appropriate ethyl 3-oxo-3H-pyridophenoxazine-2-carboxylates XIVa - XIVc.Similar reaction of XIIIa and XIIIb in aqueous solution yields mixtures of the respective ester (XIVa and XIVb, respectively) and acid (XIVd and XIVe, respectively).Compounds XIVg - XIVj were prepared by usual methods.The compounds prepared were tested for their antimicrobial activity in vitro.
