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Z. Naturforsch. 2014,
69b, 913 – 923
doi:10.5560/ZNB.2014-4107
Synthesis and Modeling Study of Some Potential Pyrimidine Derivatives as HIV Inhibitors
1 Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq
2 Department of Chemistry, College of Education, University of Basrah, Basrah, Iraq
Reprint requests to Prof. Dr. N. A. Al-Masoudi. E-mail:
najim.al-masoudi@gmx.de
Received May 20, 2014 / published online August 12, 2014
A new series of 2-amino-6-((4-aryldiazenyl)benzyloxy)-4-chloropyrimidine derivatives 4–13 and 2,6-diamino-5-arylazo-4-chloro-pyrimidine analogs 15–20 were synthesized from the pyrimidine scaffolds 3 and 14, respectively, via diazotization with various amines. Nucleophilic displacement at the 2,4-diamino-5-arylazo-6-chloro-pyrimidine 16 by different amines afforded the 4-alkylamino analogs 21–27. All new compounds were evaluated for their in vitro anti-HIV activity in MT-4 cells as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. Screening results indicated that 10 and 11 were found to be the only compounds in the series inhibiting HIV-1 replication in cell cultures with EC50 of > 1.23 and > 2.92 μg mL−1 of a CC50 of 12.30 and 17.52 μg mL−1, resulting in a selectivity index of 10 and 6, respectively. In addition, preliminary structure-activity relationships and molecular modeling of these new analogs are detailed in this manuscript.
Key words: Anti-HIV Activity, Diazotization, NNRTIs, Pyrimidines, Molecular Modeling Study