The potential antiviral activity of a novel pyrimidine derivative against Herpes Simplex Virus type-1 (HSV-1)

Abstract

Saif M. Hassan, Ashwaq Najemaldeen Abbas al-Jaf, Yasmeen Ali Hussien, Samir M. Awad, Najah R. Hadi.

Context: Previous studies and the are trials to find new molecules to help in the war against viruses. We have started preparing new compounds in this field beginning with the nucleus of thiouracil for what is known from its multiple biological activity, including against viruses. objective: Evaluation antiviral activities of new synthetic pyrimidine compounds. materials and methods: Our new target compounds were prepared starting with 2-thiouracil which was hydroxy methylated to give compound 1 which in turn was chloromethylated by thionyl chloride yielding compound 2. This chloromethyl compound was then reacted with three selected aromatic amines namely, p-nitroaniline, p-fluoroaniline and 2-aminopyridine respectively, giving aminomethyl derivatives 3a-c, which were used as starting material for preparing many target compounds by reaction firstly with ß-bromopropanoic acid affording pyrimido thiazine derivatives 4a-c. They were cyclocondensed with anthranilic acid giving pyrimido quinazoline derivatives 5a-c. In another pathway, they were reacted with ß-amino ethanol affording imidazopyrimidine derivatives 6a-c. Also, they were S-methylated by methyl iodide giving methyl thiopyrimidine derivatives 7a-c alo were cyclocondensed with ethylbromoacetate and/or chloroacetyl chloride giving isomers of thiazolopyrimidine derivatives 8a-c and 9a-c. Finally, they S-alkylated by reaction with chloroacetic acid yielding acetic acid derivatives 10a-c. Results: Compound 3c and 10c exhibited a potent antiviral activity and, they showed insignificant differences as compared with other compounds. In addition, 10c exhibited higher efficacy as compared with acyclovir. Conclusion: The aryl methyl aminopyrimidine was the pharmacophore of these target compounds. Any change in the structure decreases the activity except the introduction of acetic acid moiety which potentiate the antiviral activity.