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SYNTHESIS AND MOLECULAR MODELING OF INHIBITORS OF C-AMP PHOSPHODIESTERASE 4A IN SERIES OF HYDRAZINE DERIVATIVES OF 2-[3-METHYL-7-(THIETANYL-3)XANTHINYL-1]ACETIC AND 2-[3-METHYL-7- (THIETANYL-3)XANTHINYL-8-THIO]ACETIC ACIDS

Abstract

Reactions of ethyl 2-[8-bromo-3-methyl-7-(thietanyl-3)xanthinyl-1]acetate (1) and ethyl 2-[1-benzyl-3-methyl-7-(thietanyl-3)xanthinyl-8-thio]acetate (4) with hydrazine were investigated and hydrazine 2 and hydrazide 6 derivatives were synthesized. Reactions hydrazine 2 and hydrazide 6 with aromatic carbonyl compounds arylmethylenehydrazides 3а,b и 7а,b were obtained. The structure of the synthesized compounds was confirmed by spectroscopy. Based on the prediction of biological activity of the synthesized compounds in the PASS program we selected promising inhibitors of c-AMP phosphodiesterase, and their molecular docking with an active cAMP phosphodiesterase 4A binding site was performed. The calculated inhibition constant of cAMP phosphodiesterase 4A by compounds 2 and 7a is lower than that of pentoxifylline by 15 and 253 times, respectively, which confirms the prospectivity of the search for cAMP inhibitors of phosphodiesterase 4A in the series of hydrazine derivatives of 2-[3-methyl-7-(thietanyl-3)xanthinyl-1]acetic and 2-[3-methyl-7-(thietanyl-3)xanthinyl-8-thio]acetic acids.

About the Authors

V. A. Nebogatova
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation


M. A. Urazbaev
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation


E. E. Klen
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation


F. A. Khaliullin
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation


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Review

For citations:


Nebogatova V.A., Urazbaev M.A., Klen E.E., Khaliullin F.A. SYNTHESIS AND MOLECULAR MODELING OF INHIBITORS OF C-AMP PHOSPHODIESTERASE 4A IN SERIES OF HYDRAZINE DERIVATIVES OF 2-[3-METHYL-7-(THIETANYL-3)XANTHINYL-1]ACETIC AND 2-[3-METHYL-7- (THIETANYL-3)XANTHINYL-8-THIO]ACETIC ACIDS. Bashkortostan Medical Journal. 2018;13(2):54-59. (In Russ.)

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ISSN 1999-6209 (Print)