Synthesis of non-immunosuppressive cyclophilin-Binding cyclosporin A derivatives as potential anti-HIV-1 drugs.
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) approximately 46 nM) and low immunosuppressive activities (IC(50)>or=1500 nM).
Evers
Michel
M
Aventis Pharma S.A., Centre de Recherche de Paris, 13 quai Jules Guesde, BP 14, 94403, Vitry-sur-Seine Cedex, France.
Barrière
Jean-Claude
JC
Bashiardes
Georges
G
Bousseau
Anne
A
Carry
Jean-Christophe
JC
Dereu
Norbert
N
Filoche
Bruno
B
Henin
Yvette
Y
Sablé
Serge
S
Vuilhorgne
Marc
M
Mignani
Serge
S
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D016572:Cyclosporine / Q000138:chemical synthesis* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D016572:Cyclosporine