Synthesis And Bioactivities Of Acylthiourea Pyrimidine Derivatives

Acylthiourea pyrimidine derivatives are easy preparation and have broad biological activity, such as, insecticidal, fungicidal, weeding, and regulation of plant growth. Anti-virus activity is another important feature of these compounds, which has attracted attention of researchers, but the relevant research results are rare. Based on the potential antiviral activity of acylthiourea pyrimidines, influenza neuraminidase inhibitory activities of this type of compounds were screened, with a view to obtain influenza virus neuraminidase inhibitors with the structure of acylthiourea pyrimidine.Neuraminidase,M2 ion channel protein and Hemagglutinin,which are three kinds of envelope glycoprotein, play key roles in the life cycle of influenza viruses and are the main targets of anti-influenza drugs.Influenza viruses could be divided into A, B, C three types according to the difference between nucleoprotein proteins and membrane proteins. And according to the antigen of hemagglutinin and neuraminidase, it could be divided into different subtypes (HxNy). M2 ion channel inhibitors are only the A-effective and easy to produce drug resistance.The neuraminidase inhibitors are effective on both A type and B type, and plays important roles as anti influenza virus drugs. So the neuraminidase inhibitors become to be focused on as anti-influenza drugs.2-amino-5-bromo-4-bromomethylpyrimidine and other brominated pyrimidine interme-diates were prepared by bromination of 2-amido-4-methlpyrimidine in glacial acetic acid with bromine. Further modification of 2-amino2-bromo-4-bromomethyl pyrimidine by nucleophilic substitution to give nine 2-amino-5-bromo-4-substituted pyrimidine derivatives. The above-pyrimidine intermediates were spliced into the acylisothiocyanates structure, which were obtained by the reaction of chloride and potassium thiocyanate, to get the target acylthiourea pyrimidine compounds. The target compounds were first synthesized and verified by 1H-NMR,13C-NMR and MS. The inhibitory effect of NA was investigated. Compounds 3a,3b,5a,6a,6c exhibited moderate inhibitory activities against NA.And,the inhibitory effect of some of the target compounds on VSMC proliferation was investigated by MTT. Compound 2b.2c,2d,2e,6c exhibited moderate inhibitory activities against vascular smooth muscle cells proliferation.