The synthesis and antituberculosis activity of 5-alkynyl uracil derivatives
Yana B Platonova1, Alexander N Volov2, Larisa G Tomilova1
1Department of Chemistry, Lomonosov Moscow State University, 1 Leninskie Gory, Moscow 119991, Russian Federation; Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, Moscow Region 142432, Russian Federation.
Abstract:
A series of new 5-alkynyl-substituted uracil and uridine derivatives were synthesised via palladium-catalysed Sonogashira cross-coupling reaction of 5-bromo-pyrimidine base with terminal acetylenes with good yields in DMF at room temperature. All obtained compounds were tested for antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis (H37Ra) at concentrations of 1-100 µg/ml using MABA test. Obtained results revealed that most of tested uracil derivatives exhibited high antimycobacterial activity (MIC50 = 1.1-19.2 µg/ml) in comparison with therapeutic agents such as rifampicin, isoniazid and d-cycloserine, excluding compounds having alkyl substituent at triple alkyne bond.
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