Synthesis and diuretic properties of n-aryl- 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1h-pyrrolo [3,2,1-ij]quinoline-5-carboxamides with electron-acceptor substituents in the anilide fragment

I. V. Ukrainets, M. Yu. Golik, O. L. Shemchuk, V. M. Kravchenko


In numerous studies of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides it has been convincingly shown that amidation of quinoline-3-carboxylic acids esters with alkyl-, aryl- and hetarylamines is the best way to obtain these compounds. As a rule, syntheses proceed smoothly and efficiently under rather mild conditions. However, in those cases when for formation of amides the temperature of 120-150°C and above is applied, partial destruction of the ester fragment may occur and, as a result, it pollutes the target products with specific impurities – the corresponding 4-hydroxy-1,2- dihydroquinolin-2-ones or their analogues. Application of 1H NMR spectroscopy allows to prove that the cause of ester fragments destruction, which sometimes can be observed when alkyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates react with amines under harsh conditions, is water presented in the reagents or in the solvents. It becomes clear from this study that at the temperature of 95°C and higher the sensitivity of 4-hydroxy-2-oxo-1,2-dihydroquinoline- 3-carboxylic acids esters in a solution or a melt to hydrolysis increases significantly. Simple methods to minimize this undesirable process have been proposed – if the synthesis of N-substituted amides based on them requires such severe conditions, water should be removed from the reagents and solvents in order to avoid contamination of the final products with 4-hydroxy-1,2-dihydroquinolin-2-ones. The results of the diuretic properties study of new substituted anilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid are discussed.


anilides; 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides; pyrroloquinolines; amidation; hydrolysis; diuretic activity

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Ukrainets I.V., Gorokhova O.V., Andreeva X.V., Sim G. // Int. J. Pharm. Pharmacol. – 2012. – Vol. 1, №3. – Р. 33-40.

Jönsson S., Andersson G., Fex T. et al. // J. Med. Chem. – 2004. – Vol. 47, №8. – Р. 2075-2088.

Collin X., Robert J.M., Duflos M. et al. // J. Pharm. Pharmacol. – 2001. – Vol. 53, №3. – Р. 417-423.

Khan S.R., Mhaka A., Pili R., Isaacs J.T. // Bioorg. Med. Chem. Lett. – 2001. – Vol. 11, №4. – Р. 451-452.

Björk A., Jönsson S., Fex T., Hedlund G. / US Patent 6077851. – 2000.

Kutyrev A., Kappe T. // J. Heterocyclic Chem. – 1997. – Vol. 34, №5. – Р. 969-972.

Ukrainets I.V., Kolesnik E.V., Sidorenko L.V. et al. // Chem. Heterocycl. Comp. – 2006. – Vol. 42, №6. – Р. 765-775.

Ukrainets I.V., Mospanova E.V., Sidorenko L.V. // Chem. Heterocycl. Comp. – 2007. – Vol. 43, №7. – Р. 863-870.

Ukrainets I.V., Golik N.Yu., Shemchuk A.L. et al. // Chem. Heterocycl. Comp. – 2011. – Vol. 47, №7. – P. 826-832.

Ukrainets I.V., Bevz O.V., Mospanova E.V. et al. // Chem. Heterocycl. Comp. – 2012. – Vol. 48, №2. – P. 320-326.

Ukrainets I.V., Davidenko А.А., Mospanova E.V. et al. // Chem. Heterocycl. Comp. – 2010. – Vol. 46, №5. – P. 559-568.

Ukrainets I.V., Gorokhova O.V., Sidorenko L.V. et al. // Zh. Org. Farm. Khim. – 2005. – Vol. 3, Is. 3 (11). – P. 20-25.

Sernov L.N., Gatsura V.V. Elements of Experimental Pharmacology [in Russian]. – Moscow: Nauka, 2000. – Р. 103-104.

Mashkovskii M.D. Drugs [in Russian]. – Moscow: RIA Novaya Volna – Izd. Umerenkov, 2009. – Р. 499-500.

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