Synthesis of 2-bromomethyl-3-hydroxy-2-hydroxymethyl-propyl pyrimidine and theophylline nucleosides under microwave irradiation. Evaluation of their activity against hepatitis B virus.
Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives 1b-d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane (2) under microwave irradiation gave the corresponding acyclonucleosides 1-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)-ones 3a-d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)-ones] 4a-c, and 7,7 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline) (9). The deacetylated derivatives were obtained by the action of sodium methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was evaluated. Compound 5b showed moderate inhibition activity against HBV with mild cytotoxicity.
Ashry
E S H El
ES
Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt. eelashry60@hotmail.com
Rashed
N
N
Abdel-Rahman
A
A
Awad
L F
LF
Rasheed
H A
HA
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008872:Microwaves; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013806:Theophylline / Q000737:chemistry*
C514093:1-((2-bromomethyl-3-hydroxy-2-hydroxymethyl)prop-1-yl)-6-methyl-2-methylthiopyrimidin-4(1H)-one; D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; D011744:Pyrimidinones; D013806:Theophylline