Aventis Pharma S.A., Centre de Recherche de Paris, 13 quai Jules Guesde, BP 14, 94403, Vitry-sur-Seine Cedex, France
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 (IC50 46 nM) and low immunosuppressive activities (IC50≥1500 nM).