Synthesis and in vitro evaluation of S-acyl-3-thiopropyl prodrugs of Foscarnet. 2004

Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
Laboratoire de Chimie Biomoléculaire, UMR 5032, Université Montpellier II,ENSCM, 8 rue de l'Ecole Normale, 34296, Montpellier Cedex 5, France.

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).

UI MeSH Term Description Entries
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002264 Carboxylic Acids Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. Carboxylic Acid,Acid, Carboxylic,Acids, Carboxylic
D005069 Evaluation Studies as Topic Works about studies that determine the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. Critique,Evaluation Indexes,Evaluation Methodology,Evaluation Report,Evaluation Research,Methodology, Evaluation,Pre-Post Tests,Qualitative Evaluation,Quantitative Evaluation,Theoretical Effectiveness,Use-Effectiveness,Critiques,Effectiveness, Theoretical,Evaluation Methodologies,Evaluation Reports,Evaluation, Qualitative,Evaluation, Quantitative,Evaluations, Qualitative,Evaluations, Quantitative,Indexes, Evaluation,Methodologies, Evaluation,Pre Post Tests,Pre-Post Test,Qualitative Evaluations,Quantitative Evaluations,Report, Evaluation,Reports, Evaluation,Research, Evaluation,Test, Pre-Post,Tests, Pre-Post,Use Effectiveness
D005990 Glycerol A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, or sweetening agent. 1,2,3-Propanetriol,Glycerin,1,2,3-Trihydroxypropane,Glycerine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013438 Sulfhydryl Compounds Compounds containing the -SH radical. Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015498 HIV-2 An HIV species related to HIV-1 but carrying different antigenic components and with differing nucleic acid composition. It shares serologic reactivity and sequence homology with the simian Lentivirus SIMIAN IMMUNODEFICIENCY VIRUS and infects only T4-lymphocytes expressing the CD4 phenotypic marker. HTLV-IV,Human T-Lymphotropic Virus Type IV,Human immunodeficiency virus 2,LAV-2,HIV-II,Human Immunodeficiency Virus Type 2,Human T Lymphotropic Virus Type IV,Immunodeficiency Virus Type 2, Human,SBL-6669

Related Publications

Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
January 1998, Antiviral chemistry & chemotherapy,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
December 1980, Journal of pharmaceutical sciences,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
May 2007, International journal of pharmaceutics,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
October 2010, Molecules (Basel, Switzerland),
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
November 1984, Journal of pharmaceutical sciences,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
January 1999, Nucleosides & nucleotides,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
January 1999, Nucleosides & nucleotides,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
May 1994, Journal of pharmaceutical sciences,
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
February 1992, Farmaco (Societa chimica italiana : 1989),
Valérie Gagnard, and Alain Leydet, and Alain Morère, and Jean-Louis Montero, and Isabelle Lefèbvre, and Gilles Gosselin, and Christophe Pannecouque, and Erick De Clercq
November 2001, The Journal of pharmacy and pharmacology,
Copied contents to your clipboard!