title: 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) approximately 46 nM) and low immunosuppressive activities (IC(50)>or=1500 nM).
authors.affiliation: Aventis Pharma S.A., Centre de Recherche de Paris, 13 quai Jules Guesde, BP 14, 94403, Vitry-sur-Seine Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Evers
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Barrière
authors.forename: Georges
authors.initials: G
authors.lastname: Bashiardes
authors.forename: Anne
authors.initials: A
authors.lastname: Bousseau
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Carry
authors.forename: Norbert
authors.initials: N
authors.lastname: Dereu
authors.forename: Bruno
authors.initials: B
authors.lastname: Filoche
authors.forename: Yvette
authors.initials: Y
authors.lastname: Henin
authors.forename: Serge
authors.initials: S
authors.lastname: Sablé
authors.forename: Marc
authors.initials: M
authors.lastname: Vuilhorgne
authors.forename: Serge
authors.initials: S
authors.lastname: Mignani
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D016572:Cyclosporine