European Journal of Chemistry 2014, 5(4), 588-594 | doi: https://doi.org/10.5155/eurjchem.5.4.588-594.1109 | Get rights and content






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


Yossra Abood Marich (1) , Niran Jassim Al-Salihi (2) , Najim Aboud Al-Masoudi (3,*)

(1) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(2) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(3) Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq
(*) Corresponding Author

Received: 15 Jun 2014 | Accepted: 08 Jul 2014 | Published: 31 Dec 2014 | Issue Date: December 2014

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.


Keywords


Pyrimidines; Anti-HIV activity; Sodium hypochlorite; Molecular modeling study; Structure activity relationship; Non-nucleoside reverse transcriptase inhibitors

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DOI: 10.5155/eurjchem.5.4.588-594.1109

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Department of Chemistry, College of Science, University of Basrah, Basrah, 61001, Iraq

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How to cite


Marich, Y.; Al-Salihi, N.; Al-Masoudi, N. Eur. J. Chem. 2014, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Y.; Al-Salihi, N.; Al-Masoudi, N. Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues. Eur. J. Chem. 2014, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Y., Al-Salihi, N., & Al-Masoudi, N. (2014). Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues. European Journal of Chemistry, 5(4), 588-594. doi:10.5155/eurjchem.5.4.588-594.1109
Marich, Yossra, Niran Jassim Al-Salihi, & Najim Aboud Al-Masoudi. "Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues." European Journal of Chemistry [Online], 5.4 (2014): 588-594. Web. 29 May. 2020
Marich, Yossra, Al-Salihi, Niran, AND Al-Masoudi, Najim. "Synthesis, anti-HIV activity and molecular modeling study of some new pyrimidine analogues" European Journal of Chemistry [Online], Volume 5 Number 4 (31 December 2014)

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