Chemical modifications of 6-allylsulfonyl- 4-methyl-1,2-dihydroquinolin-2-one as the approach for seaching new biologically active substances
DOI:
https://doi.org/10.24959/nphj.14.1977Keywords:
1, 2-dihydroquinoline-2-one, allylsulfone, heterocyclic sulfones, nucleophilic additionAbstract
To search biologically active substances among quinolone-2 sulfonyl derivatives the method for obtaining of the convenient intermediate, namely 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one, has been developed. The synthesis has been carried out by alkylation of the initial 4‑methyl-2-oxo- 1,2-dihydroquinoline-6-sulfinic acid with allyl bromide in the acetonitrile medium and in the presence of potassium carbonate giving 73% yield of the product. The presence of the allyl fragment of 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one allowed to carry out addition reactions with some C-, N- and O-nucleophiles. Addition to allyl sulfones occurs in accordance with Markovnikov’s rule despite of the strong electron withdrawing effect of the sulfonyl group. The reaction of 6‑allylsulfonyl- 4-methyl-1,2-dihydroquinoline-2-one with active methylene compounds has been carried out with diethyl malonate and ethyl cyanoacetate by refluxing in absolute ethanol in the presence of sodium ethoxide. As a result, 2-R-3-methyl-4-(4-methyl-2-оxo-1,2-dihydroquinoline-6-sulfonyl)butanoic acid ethyl esters have been obtained with 73-79% yields. 6-(2 Alkylaminopropylsulfonyl)-4-methyl-1,2- dihydroquinoline-2-ones are formed under the action of N-nucleophilic reagents, in particular primary aliphatic amines, on 6-allylsulfonyl-4-methyl-1,2-dihydroquinoline-2-one. This reaction takes place upon heating in dimethylformamide up to 50-60oC for 6 hours, the yields of the products are 35-40%. Hydration of the allyl fragment occurs in the same solvent when treated with sodium hydroxide at 20oC resulting in formation of 6-(2-hydroxypropylsulfonyl)-4-methyl-1,2-dihydroquinolin-2-one with 62% yield. The chemical transformations described open a prospect for synthesis of variety of new compounds with different functional groups in the alkylsulfonyl moiety of quinolones. This approach also allows to influence on such properties of new biologically active substances as molecular weight, lipophilicity, acidity, etc., which are essential for permeability of substances through biological membranes.
References
Зубков В.О., Гриценко І.С., Цапко Т.О. // ЖОФХ. – 2009. – Т. 7, вип. 3 (27). – С. 30-34.
Зубков В.А., Цапко Т.А., Гриценко И.С., Малоштан Л.Н. // ИзвАН. Серия хим. – 2010. – №12. – С. 2272-2275.
Получение и свойства органических соединений серы / Под ред. Л.И.Беленького. – М.: Химия, 1998. – 560 с.
Прилежаева Е.Н. // Успехи химии. – 2000. – Т. 69, №5. – С. 403-446.
Amewu R., Gibbons P., Mukhtar A., Stachulski A.V. et al. // Org. Biomolec. Chem. – 2010. – №8 (9). – Р. 2068-2077.
Cohen A., Crozet M.D., Rathelot P. // Molecules. – 2012. – Vol. 21, №18 (1). – P. 97-113.
Oja S., Saransaari P. // Proc. West. Pharmacol. Soc. – 2007. – Vol. 50. – Р. 8-15.
Padmavathi V., Thriveni P., Sudhakar Reddy G., Deepti D. // Eur. J. Med. Chem. – 2008. – Vol. 43, №5. – P. 917-924.
Samuele A., Kataropoulou A., Viola M., Zanoli S. et al. // Antiviral Res. – 2009. – Vol. 81, №1. – P. 47-55.
Shaaban M.R., Saleh T.S., Mayhoub A.S., Mansour A. et al. // Bioorg. Med. Chem. – 2008. – Vol. 16, №12. – P. 6344-6352.
Silvestri R., De Martino G., La Regina G. et al. // J. Med. Chem. – 2005. – Vol. 46, №12. – P. 2482-2493.
Tozkoparan B., Küpeli E., Yeşilada E., Ertan M. // Bioorg. Med. Chem. – 2007. – Vol. 15, №4. – P. 1808-1814.
Verbist B., Cleyn M., Surkyn M., Fraiponts E. et al. // Bioorg. Med. Chem. Lett. – 2008. – Vol. 18, №8. – P. 2574-2579.
Downloads
Published
Issue
Section
License
Copyright (c) 2014 National University of Pharmacy
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).