Synthesis, anti-17β-HSD and antiproliferative activity of new substituted 5-nitrosopyrimidine analogs

A new series of 2-amino-4-alkylamino-6-methylamino-5-nitrosopyrimidine derivatives 10–14 have been synthesized from 5-nitrosopyrimidine analog 9 by nucleophilic aromatic substitution reaction with various amines using dimethylformamide as a solvent at 70–90 °C. Similarly, various 4-alkylamino-5-nitrosopyrimidine analogs 16–24 were obtained from 9 and primary and secondary amines using dichloromethane at room temperature. Analogously, treatment of 9 with 2-thioglycolic acid afforded 4-thioalkyl derivative 15. Treatment of 9 with chloroacetyl chloride (26) gave the corresponding chloroacetamido analog 27, which afforded the desired 2-(benzothiazol-2-ylthio)-N-(4-isopropoxy-6-(methylamino)-5-nitrosopyrimidine-2-yl)acetamide (29) on treatment with 2-mercaptobenzothiazole (28) in the presence of triethylamine and dichloromethane. Condensation of 9 with butyraldehyde in acidic ethanol gave the corresponding 2-butylideneamino analog 30. Selected examples of the synthesized compounds were evaluated for their 17β-hydroxysteroid dehydrogenase type 1 and 2 (17β-HSD1 and 2) inhibitory activity. Futhermore, same compounds were evaluated for their antiproliferative activity against two solid tumour-derived cell lines consisting Hep-G2 (human hepatocarcinoma) and MCF-7 (breast cancer).