Synthesis and the antimicrobial activity of ethyl 3-alkyl-2-(alkylthio)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate derivatives

S. V. Vlasov, V. P. Chernykh, T. P. Osolodchenko

Abstract


The effective method for the synthesis of ethyl 3-alkyl-5-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylate derivatives by interaction of diethyl 3-methyl-5-{[(methylsulfanyl)carbothioyl]amino}thiophene-2,4-dicarboxylate with low aliphatic amines in the 2-propanol medium has been developed. The conditions proposed facilitate isolation and perceptibly improve the yields of the target thiones. The further modification of ethyl 3-alkyl-5-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylate has been performed by alkylation with chloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles (DMF-triethylamine). The structure of the compounds obtained has been confirmed using the NMR spectroscopic methods; the products of alkylation have the signals of the carbethoxy group as two signals in the ranges of 1.27-1.30 ppm (3H, t) and 4.24-4.29 (2H, q), and the signal of SCH2 protons in the range of 4.22-4.93 ppm. The study of the antimicrobial activity for the functionalized derivatives of thieno[2,3-d]pyrimidine, the corresponding ethyl 3-alkyl-5-methyl-2-({2-[arylamino]-2-oxoethyl}thio)-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylates and ethyl 3-alkyl-5-methyl-4-oxo-2-{[(3-aryl-1,2,4-oxadiazol-5-yl)methyl]thio}-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylate has shown their moderate antimicrobial properties, while for some compounds with the n-butyl substituent at position 3 possess the high inhibitory activity against Candida albicans fungi growth.


Keywords


thiophene; pyrimidine; mercaptans; alkylation; cyclization

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References


Коваленко С.Н., Власов С.В., Федосов А.И., Черных В.П. // Журнал органічної та фармацевтичної хімії. – 2007. – Т. 5, №3. – С. 34-40.

Alagarsamy V., Meena S., Ramseshu K.V. et al. // Eur. J. Med. Chem. – 2006. – Vol. 41, № 11. – P. 1293 – 1300.

Alagarsamy V., Solomon V.R., Deepa G. et al. // Arch. Pharm. – 2007. – Vol. 340, № 7. – P. 352 - 358.

American Society for Microbiology. Manual of Antimicrobial Susceptibility Testing. American Society for Microbiology: Washington. 2005. – P. 236.

Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. Document M100-S22, Vol. 32, No. 3, CLSI, Wayne, PA, January, 2012.

Hafez H.N., El-Gazzar A.-R.B.A., Nawwar G.A.M. // Eur. J. Med. Chem. – 2010. – Vol. 45, №4. – P. 1485-1493.

Hussein H.A.R. // Phosphorus, Sulfur, Silicon and Relat. Elem. – 2007. – Vol. 182, №9. – P. 2069-2085.

Ivachtchenko A.V., Kovalenko S.M., Tkachenko O.V., Parkhomenko O.O. // J. Comb. Chem. — 2004. — Vol. 6, № 4. — Р. 573-583.

Lipinski C. A. // Drug Discov. Today: Tech. – 2004. – Vol. 1, №4. – P. 337-341.

Pat. US 2007197551 (2007) // Заявл.: 25.02.2005; опубл.: 23.08.2007. http://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20070823&DB=EPODOC&locale=en_EP&CC=US&NR=2007197551A1&KC=A1&ND=4.

Pathak U.S., Rathod I.S., Jain K.S. et al. // Indian J. Chem. –1997. – Vol. 36B. – P. 566-571.

Tkachenko O.V., Vlasov S.V., Kovalenko S.M. et al. // Жур¬нал органічної та фармацевтичної хімії. – 2013. – Т. 11, №3 (43). – С. 9-15.

Vlasov S.V., Kovalenko S.M., Osolodchenko T.P., Chernykh V.P. // Вісник фармації. – 2015. – №1 (81). – С. 6-10.


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DOI: https://doi.org/10.24959/88863

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)