There is an urgent need for the design and development of new and safer drugs for the treatment of HIV infection, active against the currently resistant viral strains. New derivatives of the non-steroidal anti-inflammatory drug indomethacin bearing benzimidazoles, benzothiazole, purine and pyridine residues 8 -13 were synthesized with the aim of developing new non-nucleoside reverse transcriptase inhibitors (NNRTIs). Alternatively, new imine analogs 16 -20 were synthesized from condensation of indomethacinyl hydrazide 15, prepared from the ester 14, with various ketone precursors. Treatment of 15 with phenyl isothiocyanate or triethyl orthoformate afforded the phenylcarbonothioyl and the oxadiazole derivatives 21 and 22, respectively. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 9 and 10 were the most active in inhibiting HIV-2 and HIV-1, respectively, with EC 50 ≥ 17.60 µg mL −1 and > 1.15 µg mL −1 (therapeutic indexes (SI) of ≥ 3 and < 1, respectively), and are leading candidates for further development.

Structural modification of these compounds might optimize their anti-HCV activity by introducing diverse and potent functional groups at the pyrimidine backbone, like nitrile residue. Because of the nature of the molecules, these new derivatives will also be evaluated for their potential anti-HIV activity.

Objective: 4-methoxy-N, N-dimethyl-6-(phenylthio) pyrimidin-2-amine, 4-(benzo [d]thiazol-2-ylthio)-6-methoxy-N,N-dimethylpyrimidin-2-amine, 4-(4-(1,2,3-selenadiazol-4-yl)phenoxy)-6-methoxy-N,N-dimethylpyrimidin-2-amine and 4-(4-(1,2,3-thiadiazol-4-yl)phenoxy)-6-methoxy-N,N-dimethylpyrimidin-2-amine have been synthesized. Method: The prepared compounds were synthesized by nucleophilic displacement of chloride substituted in pyrimidine heterocyclic ring. Results: The synthesized compounds were being identified by different methods included TLC technique, IR, 1H-NMR and 13C-NMR spectrophotometers. All compounds confirmed by elemental analysis. The biological activity of these new compounds investigated against some fungi like Aspergillus terreus and Aspergillus niger, the results was Aspergillus terreus more effected by antifungal compare with Aspergillus niger, the effect ration 0.98, 1.32 with 200µM respectively and the compound number (2) has more effect than other compounds. Conclusion: It is concluded that synthesized dimethylpyrimidin-derivatives are biologically active and developed into useful Antifungal agents. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Pyrimidine is a prominent member of the diazine family of heterocyclics. It is found throughout nature as a component of nucleic acids, nucleotides and corresponding nucleosides. Pyrimidine was first isolated by Gabriel and Colman in 1899 1. Pyrimidine represents one of the most active class of compounds possessing wide spectrum of biological activity viz. significant in vitroactivity against unrelated DNA and RNA, viruses including polio herpes viruses, diuretic, antitumor, anti HIV, cardiovascular 2. Methoprim, 5-(3,4,5trimethoxybenzyl) pyrimidine-2,4-diamine (1) 3 , is a potent and interesting pyrimidine analogue was used, since 1980, in combination with sulfamethoxazole as a bacteriostaticantibiotic (Co-trimoxazole) and

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