112811-66-2Relevant articles and documents
Practical synthesis and molecular structure of a potent broad-spectrum antibacterial isothiazoloquinolone
Hashimoto, Akihiro,Pais, Godwin C. G.,Wang, Qiuping,Lucien, Edlaine,Incarvito, Christopher D.,Deshpande, Milind,Bradburyand, Barton J.,Wiles, Jason A.
, p. 389 - 398 (2007)
We report the synthesis of the new 2-sulfonylquinolone ethyl 1-cyclopropyl-6,7-difluoro-2-methanesulfonyl-8-methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylate (5). Sulfone 5 is a key intermediate used in the optimized synthesis of the isothiazoloquinolone 9-cyclopropyl-6-fluoro-8- methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4-b]quinoline-3,4-dione (1), a potent broad-spectrum antibacterial agent that is effective against clinically important resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA). Our synthetic method is free of chromatographic purification and amenable to large-scale synthesis. The molecular structures of 1, 9-cyclopropyl-6,7-difluoro-8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-dione (4), 5, and ethyl 2-cyclopropylamino-6,7-difluoro-8-methoxy-4-oxo-4H- thiochromene-3-carboxylate (10) were established unambiguously using multinuclear NMR spectroscopy and X-ray crystallography.
COMPOUNDS TARGETING RNA-BINDING PROTEINS OR RNA-MODIFYING PROTEINS
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Page/Page column 59; 60, (2021/09/11)
The invention relates to a compound represented by Formula (I): or a pharmaceutically acceptable salt thereof, compositions comprising the same and methods of preparing and using the same. The variables are described herein.
Identification of an ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate as a catalytic inhibitor of DNA gyrase
Aguirre, Arturo L.,Chheda, Pratik R.,Groves, Natalie P.,Held, Hailey A.,Hiasa, Hiroshi,Kerns, Robert J.,Lentz, Sarah R. C.
, (2020/04/02)
Fluoroquinolones are a class of antibacterial agents used clinically to treat a wide array of bacterial infections and target bacterial type-II topoisomerases (DNA gyrase and topoisomerase IV). Fluoroquinolones, however potent, are susceptible to bacterial resistance with prolonged use, which limits their use in the clinic. Quinazoline-2,4-diones also target bacterial type-II topoisomerases and are not susceptible to bacterial resistance similar to fluoroquinolones, however, their potency pales in comparison to fluoroquinolones. To meet the increasing demand for antibacterial development, nine modified quinazoline-2,4-diones were developed to probe quinazoline-2,4-dione structure modification for possible new binding contacts with the bacterial type-II topoisomerase, DNA gyrase. Evaluation of compounds for inhibition of the supercoiling activity of DNA gyrase revealed a novel ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate derivative as a modest inhibitor of DNA gyrase, having an IC50 of 3.5 μM. However, this ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate does not trap the catalytic intermediate like fluoroquinolones or typical quinazoline-2,4-diones do. Thus, the ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate derivative discovered in this work acts as a catalytic inhibitor of DNA gyrase and therefore represents a new structural type of catalytic inhibitor of DNA gyrase.
Novel fluoroquinolones and use thereof to treat bacterial infections
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Paragraph 0063; 0065, (2016/01/12)
The present invention relates to novel fluoroquinolones possessing a piperazine moiety substituted by a long alkyl chain, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.
