Synthesis, Structure, and In Vitro Anti-HIV Activity of New Pyrazole, 1,2,4-Thiadiazole, and 1,2,4-Triazole Derivatives

Abstract

α,α′-Dichloroazo compounds 6 react with Lewis acid to furnish 1-(chloroalkyl)-1-aza-2-azoniaallene salts 4. The cations 4 react with acetylenes, isothiocyanates, isocyanates, and carbodiimides under [3+2]-cycloaddition. The cycloadducts undergo consecutive reactions, e.g., [1,2]-shifts of alkyl groups. The newly synthesized products were evaluated for their anti-HIV-1 and anti-HIV-2 activity in MT-4 cells.

Keywords:

• 1,2,4-Thiadiazolse
• 1,2,4-Triazole
• NNRTIs
• pyrazoles
• synthesis

Acknowledgments

This work was supported by the DAAD (Deutscher Akademischer Austausch Dienst). We thank Professor N. Al-Masoudi, Konstanz, Germany, for helpful discussion, as well as Professors E. De Clercq and C. Pannecouque, Rega Institute for Medical Research, Belgium, for the anti-HIV screening.

Notes

^a Anti-HIV-1 activity measured with strain III _B .

^b Anti-HIV-2 activity measured with strain ROD.

^c Compound concentration required to achieve 50% protection of MT-4 cells from the HIV-1- and 2-induced cytopathogenic effect.

^d Compound concentration that reduces the viability of mock-infected MT-4 cells by 50%.

^e SI: Selectivity index (CC₅₀/EC₅₀).