European Journal of Chemistry

Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues

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Published: Dec 31, 2014
DOI: https://doi.org/10.5155/eurjchem.5.4.588-594.1109
Keywords:
Pyrimidines, Anti-HIV activity, Sodium hypochlorite, Molecular modeling study, Structure activity relationship, Non-nucleoside reverse transcriptase inhibitors
Section
Research Article
Issue
Vol. 5 No. 4 (2014): December 2014
Dates
Received 2014-06-15
Accepted 2014-07-08
Published 2014-12-31


Main Article Content

Yossra Abood Marich
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
Niran Jassim Al-Salihi
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
Najim Aboud Al-Masoudi
Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq

Abstract

A new series of 2,6-diamino-5-arylazo-4-chloropyrimidine analogues (6-13) were synthesized from the pyrimidine scaffold 5, via diazotization with various amines. Nucleophilic displacement of compound 5 by ethanethiolate or arylthio nucleophiles, afforded the 4-alkylthio analogues (14-16). Treatment of compound 17 or 18 with thiourea under MWI gave the 4-thione derivatives 19 and 20, respectively. On treatment of compound 20 with 2-mercaptoacetic acid furnished the 4-thio analogue (21). Reaction of compound 19 or 20 with sodium hypochlorite followed by ammonium hydroxide afforded the 4-aminothio analogues 22 and 23, respectively. Oxidation of compound 23 with H2O2 led to the 4-sulphonamide derivative 24. All new compounds were evaluated for their in vitro antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. Compounds 14-16 and 21 showed an EC50 values of > 2.12, 1.99, 1.80 and 1.92 μg/mL, respectively. In addition, preliminary structure-activity relationship and molecular modeling of compound 15 has been studied.


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Marich, Y. A.; Al-Salihi, N. J.; Al-Masoudi, N. A. Synthesis, Anti-HIV Activity and Molecular Modeling Study of Some New Pyrimidine Analogues. Eur. J. Chem. 2014, 5, 588-594.

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