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.
BACTERIAL TOPOISOMERASE I INHIBITORS WITH ANTIBACTERIAL ACTIVITY
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Paragraph 0121, (2018/04/13)
The present invention provides compounds as bacterial topoisomerase inhibitors with antibacterial activity. The present invention also provides pharmaceutical compositions comprising at least one of the compounds and methods of using the compounds and pharmaceutical compositions as antibacterial agents for treating infectious diseases.
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.
Process to obtain benzoxazines to be used for the synthesis of ofloxazine, levofloxazine and derivatives
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, (2008/06/13)
A process to obtain benzoxazines useful for the synthesis of Ofloxazine, Levofloxazine and derivatives. The benzoxacines (I) where Xb is an halogen and R1 is H, alkyl or alkenyl of up to 6 atoms of C or aryl, can be obtained by means of cycling a compound of formula (II) through the reaction with triphenylphosphine and ethyl azodicarboxilate. The compounds of formula (II) can be obtained through the reaction of a compound (III) with an adequate epoxide. Through the use of the adequate chiral epoxide it is possible to obtain the enantiomerically desired intermediate and, therefore and selectively, it is possible to obtain the desired final product with the adequate enantiomeric form without the need to carry out a resolution stage. The Compounds (I) are useful and key intermediates for the synthesis of the antimicrobials Oflixazine and Levofloxazine. STR1
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.
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.
