Synthesis and Reactions of Some New Polynuclear Heterocyclic Compounds Containing Nitrogen, Sulfur and Some Related Acyclic Nucleosides with Expected Biological Activity

Abstract

The research group which Iam a member of, has an interest in the synthesis of heterocyclic compounds containing fused pyrimidone system with the aim of obtaining biologically active compounds. Thiouracil derivatives are an important class of heterocyclic compounds, containing nitrogen and sulphur atoms, which are interesting from the chemical and biological point of view.

This following synthetic work is classified into three main sections: In Section A: we discuss for one-pot synthesis to give the target a single regioisomer 3-amino-2-hydroxy-thiazolo[3,2-a]pyrimidin-5-one derivative (17) not 23 in a good yield. 3-amino-2-hydroxy-thiazolo[3,2-a]pyrimidin-5-one derivative (17) was synthesized as a trial to obtain anti-cancer agents with potent PARP- 1 inhibition activity for treatment of breast cancer.

In Section B : synthesis of 3-amino-2-hydrazinyl-thiazolo[3,2-a]pyrimidin-5-one derivative (26) by direct hydrazinolysis of compound 17 with hydrazine hydrate. The key compound 26 used for the preparation of Pyrimido-thiazolo[4,5-e][1,2,4]triazin-6-one derivative (27) and 8-methyl-pyrimido[2',1':2,3]thiazolo[4,5-e][1,2,4]triazin-6-one derivative (28). pyrimido-thiazolo[4,5-e][1,2,3,4]tetrazin-9-one derivative (29) produced by reaction with nitrous acid. Ethyl -3-(2-(3-amino-thiazolo[3,2-a]pyrimidin-2-yl) hydrazono) butanoate (31) and N'-(3-amino-thiazolo[3,2-a]pyrimidin-2-yl)-2-cyanoacetohydrazide (37) resulted by condensation reaction with ethylacetoacetate or ethylcyanoacetate in absolute ethanol. 2-Pyrazolyl derivatives 30, 34 and 39 furnished by cyclo condensation reaction with acetyl acetone , ethylacetoacetate or ethylcyanoacetate, respectively. The Schiff's basis (36a-f) are resulted also as shown in (Scheme A). 2-amino-2-hydrazino derivative (26) was synthesized as a trial to obtain anti-cancer agents with potent PARP- 1 inhibition activity for treatment of breast cancer.