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.
Pyrido(3,2,1-IJ)-1,3,4 benzoxadiazine derivatives
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, (2008/06/13)
The invention is concerned with tricyclic compounds of the formula STR1 wherein R1 is a hydrogen atom or a carboxy-protecting radical; R2 is a hydrogen atom or a lower alkyl radical which may be substituted with a halogen atom; R3 and R4 independently are a hydrogen atom or a lower alkyl radical which may be substituted with a hydroxy radical or a substituted or unsubstituted amino radical; X is a halogen atom; and R5 and R6 are independently a hydrogen atom or a lower alkyl radical which may be substituted with a hydroxy radical, a lower alkoxy radical or a substituted or unsubstituted amino radical; or R5 and R6, taken together with the adjacent nitrogen atom, may form a 5 to 7 membered heterocyclic ring which may be substituted with one or more substituents at the carbon atom(s), and the heterocyclic ring may further contain --NR7 --, --O--, --S--, --SO--, --SO2 -- or --NR7 --CO--, and also R7 is a hydrogen atom, a lower alkenyl radical, a lower alkyl or aralkyl radical which may be substituted, or a radical represented by the formula in which n is an integer from 0 to 4 and R8 is a hydrogen atom, a lower alkoxy radical, or an amino, lower alkyl or aryl radical which may be substituted, as well as pharmaceutically acceptable salts thereof, and hydrates or solvates of the compounds of the formula I or their salts. Also included is a process for the manufacture of these compounds, pharmaceutical preparations containing them, intermediates useful in said process, and methods of using them. The end products have antimicrobial activity.
