Pyrimidinthiones (Part I): Utility of 2-Thioxopyrimidin-6-(1H)ones as Ring Transformer in the Synthesis of Fused Bi- and Tri-Cyclic Heterocyclic Compounds and Their Potential Biological Activities

Abstract

The pyrimidinethiones have wide biological and pharmaceutical activities, that have attracted considerable interest in recent years especially as antiviral inhibiting production of hepatitis B virus (HBV), and in vitro insulin-mimetic. Activity of the complexes of pyrimidinone derivatives evaluated from 50% inhibitory concentration promoted us to study the transformation of the 2-thioxopyrimidin-6(1H) ones to fused bi- and tri-cyclic heterocyclic compounds having the pyrimidine moieties and screening their biological activity.

The reactivity of 2-mercapto-4-aryl-5-cyanopyrimidin-6(1H)ones (1) towards alkylation by different mono and bifunctional halo-organic compounds has been investigated to give S-monoalkylated products 2, 7 and 9; S- and N-dialkylated products 3, 13 and 14. Treatment of 1 and/or 2 with hydrazine hydrate as a nitrogen nucleophile have been investigated to give 4, treatment of 4 with CS₂ and sodium nitrite in the presence of acetic acid (0°C) produced 1,2,4-triazolopyrimidin-5(1H)one derivatives (5)and tetrazolo[1,5-a]pyrimidin-5(1H)ones (6), respectively. Also cyclization of 7 and 9 gave [1,3]thiazolo[3,2-a]pyrimidin-5(1H)one and [1,3]thiazolo[3,2-a]pyrimidin-3,5-dione derivatives 8 and 10 respectively, treatment of 10 with aromatic aldehyde produces 11 which reacted with guanidine HCl to give pyrimido[4,5-d]thiazolo[3,2-a]pyrimidin-6(1H)one derivative 12. Reaction of 14 with o-phenylenediamine was investigated and gave [1,4]quinoxalino[2,3-b][1,3]thiazolo[3,2-a]pyrimidin-9(1H)one derivative 15.

Keywords:

• Biological activity
• pyrimido[4,5-d]thiazolo[3,2-a]pyrimidinone
• quinoxalino [2,3-b]thiazolo[3,2-a]pyrimidinone
• tetrazolo[1,5-a] pyrimidinone
• thiazolo[3,2-a]pyrimidinone

Acknowledgments

The authors would like to express their appreciation and are grateful to both Prof. Dr. Sief El-Din Ashour and his assistants in the Microbiology Department, Faculty of Pharmacy, El-Azhar University for achievement of biological activities evaluation of some newly synthesized compounds and Professor Dr. K. P. Zeller, Institute fur Organische Chemie, Tubingen University, Germany for performing some ¹H and ¹³C NMR and mass spectra.