The search for new antimicrobial agents from the substituted arylamides of 4-(4-oxo-4H-quinazolin-3-yl)-piperidine-1-carboxylic acids

K. Yu. Krolenko, S. V. Vlasov, I. O. Zhuravel, T. P. Osolodchenko

Abstract


The methods for the synthesis of the substituted arylamides of 4-(4-oxo-4H-quinazolin-3-yl)-piperidine-1-carboxylic acids using the technologies of the liquid-phase parallel synthesis have been developed. The structure of the compounds obtained has been confi rmed by the data of the instrumental methods of organic analysis. The antibacterial activity of the compounds obtained has been studied using the agar “well” diffusion method against the standard test-strains of microorganisms. The results of the screening performed have shown that all compounds inhibit the growth of Staphylococcus aureus and Bacillus subtilis strains. The strains of Proteus vulgaris and Pseudomonas aeruginosa have been found to be the most resistant. The SAR-analysis of the substituted arylamides of 4-(4-oxo-4H-quinazolin-3-yl)-piperidine-1-carboxylic acids has demonstrated that the presence of the electron-donating substituents in position 8 of the quinazolin-4-one cycle and in position 4 of the aromatic fragment of the urea increases the activity of the compounds of this series against gram-positive bacteria. Such high effi cacy of the lead compounds against the gram-positive bacterial strains can be applied for creating the narrow spectrum antibiotics derived from arylamides of 4-(4-oxo-4H-quinazolin-3-yl)-piperidine-1-carboxylic acids.

Keywords


quinazoline; piperidine; ureas; antimicrobials

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References


Пат. WO2006/117762 (2007). Заявл.: 03.05.2006. Опубл.: 08.02.2007. [Электронный ресурс]. Режим доступа http://worldwide.espacenet.com/

publicationDetails/originalDocument?CC=WO&NR=2006117762A3&KC=A3&FT=D&ND=&date=20070208&DB=&&locale=en_EP.

Пат. US20130090326 (2013). Заявл.: 15.10.2010. Опубл.: 11.04.2013. [Электронный ресурс]. Режим доступа http://worldwide.espacenet.com/

publicationDetails/originalDocument?CC=US&NR=2013090326A1&KC=A1&FT=D&ND=&date=20130411&DB=&&locale=en_EP.

Samala G., Devi P. B., Nallangi R., Sridevi J. P., Saxena S., Yogeeswari P., Sriram D. Biorg. Med. Chem., 2014, Vol. 22, No.6, pp.1938-1947.

Zheng P., Somersan-Karakaya S., Lu S., Roberts J., Pingle M., Warrier T., Little D., Guo X., Brickner S. J., Nathan C. F. J. Med. Chem., 2014, Vol. 57, No.9,

pp. 3755-3772.

Пат. WO2010103381 (2010). Заявл.: 10.03.2010. Опубл.: 16.09.2010. [Электронный ресурс]. Режим доступа http://worldwide.espacenet.com/

publicationDetails/originalDocument?CC=WO&NR=2010103381A1&KC=A1&FT=D&ND=&date=20100916&DB=&&locale=en_EP.

Christodoulou M. S., Fokialakis N., Passarella D., García-Argáez A. N., Gia O. M., Pongratz I., Dalla Via L., Haroutounian S. A. Biorg. Med. Chem., 2013,

Vol. 21, No.14, pp. 4120-4131.

Пат. US8691993 (2014). Заявл.: 06.12.2012. Опубл.: 08.04.2014. [Электронный ресурс]. Режим доступа http://worldwide.espacenet.com/

publicationDetails/originalDocument?CC=US&NR=8691993B2&KC=B2&FT=D&ND=&date=20140408&DB=&&locale=en_EP.

Пат. WO2012087938 (2012). Заявл.: 19.12.2011. Опубл.: 28.06.2012. [Электронный ресурс]. Режим доступа https://patentscope.wipo.int/

search/en/detail.jsf?docId=WO2012087938.

Власов С. В., Кроленко К. Ю., Журавель И. А., Коваленко С. Н. Вестник КазНМУ, 2015, No.3, pp.232-236.

Chikkulapalli A., Aavula S. K., Mona N. P. R., Karthikeyan C., Vinodh Kumar C. H., Sulur G. M., Sumathi, S. Tetrahedron Lett., 2015, Vol. 56, No.24,

pp.3799-3803.

Anandan S.-K., Gless R. D. Bioorg. Med. Chem. Lett., 2010, Vol. 20, No.9, pp.2740-2744.

Kołaczek A., Fusiarz I., Ławecka J., Branowska D. CHEMIK, 2014, Vol. 68, No.7, pp.620-628.

Bhattacharyya S., Pathak U., Mathur S., Vishnoi S., Jain R. RSC Adv., 2014, Vol. 4, No.35, pp.18229-18233.

Chaturvedi D. Tetrahedron, 2012, Vol, 68, No.1, pp.15-45.

American Society for Microbiology, Coyle M.B. Manual of Antimicrobial Susceptibility Testing. American Society for Microbiology: Washington,

, p.236.

Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement.

Document M100-S22, 2012, Vol. 32, No.3, CLSI, Wayne, PA, January.

McFarland J. Journal of the American Medical Association, 1907, Vol. 49, No.14, pp.1176-1178.


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DOI: https://doi.org/10.24959/ophcj.16.877

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)