title: Synthesis and in vitro evaluation of S-acyl-3-thiopropyl prodrugs of Foscarnet.
abstract: A new enzyme-labile group called S-acyl-3-thiopropyl group (SATP) has been synthesized from allylic esters of phosphonate. After demonstration of the enzyme-labile character of the SATP in cellular extracts, it has been introduced onto the phosphonate moiety of PFA (Foscarnet) to obtain potential lipophilic prodrugs. To ponder the lipophilicity of the triesters of PFA, esters of monomethylether of polyethyleneglycols and of thioglycerol were introduced on the PFA carboxylate moiety. The SATP groups were introduced in an attempt to deliver PFA after bioactivation inside the cells. The PFA prodrugs were evaluated in vitro for their activity against human immunodeficiency viruses (HIV-1 and HIV-2).
authors.affiliation: Laboratoire de Chimie Biomoléculaire, UMR 5032, Université Montpellier II,ENSCM, 8 rue de l'Ecole Normale, 34296, Montpellier Cedex 5, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gagnard
authors.forename: Alain
authors.initials: A
authors.lastname: Leydet
authors.forename: Alain
authors.initials: A
authors.lastname: Morère
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montero
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lefèbvre
authors.forename: Gilles
authors.initials: G
authors.lastname: Gosselin
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erick
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism; D005069:Evaluation Studies as Topic; D017245:Foscarnet / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D063065:Organophosphonates / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002264:Carboxylic Acids; D063065:Organophosphonates; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D017245:Foscarnet; D011092:Polyethylene Glycols; C009465:thioglycerol; D005990:Glycerol