Synthesis of non-immunosuppressive cyclophilin-Binding cyclosporin A derivatives as potential anti-HIV-1 drugs

Abstract Original cyclosporin A (CsA) derivatives bearing various alkylthio side chains at the sarcosine residue 3 ( R configuration) and for the most potent and selective compounds a 4′-hydroxyl group at the Me-Leucine residue 4 were prepared in one or two steps from commercially available CsA. The [2-(dimethyl or diethylamino)-ethylthio-Sar] 3 -[(4′-OH)MeLeu] 4 -CsA derivatives 3k and 3l displayed potent in vitro anti-HIV-1 (IC 50 ∼46 nM) and low immunosuppressive activities (IC 50 ≥1500 nM).