Parallel synthesis, molecular modelling and further structure-activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
Identifieur interne : 002A60 ( Main/Curation ); précédent : 002A59; suivant : 002A61Parallel synthesis, molecular modelling and further structure-activity relationship studies of new acylthiocarbamates as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
Auteurs : Andrea Spallarossa [Italie] ; Sara Cesarini ; Angelo Ranise ; Silvia Schenone ; Olga Bruno ; Alberto Borassi ; Paolo La Colla ; Margherita Pezzullo ; Giuseppina Sanna ; Gabriella Collu ; Barbara Secci ; Roberta LoddoSource :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2009.
Descripteurs français
- KwdFr :
- Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Liaison aux protéines, Modèles moléculaires, Mutation faux-sens, Relation structure-activité, Simulation numérique, Thiocarbamates (pharmacologie), Thiocarbamates (synthèse chimique), Transcriptase inverse du VIH (antagonistes et inhibiteurs), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique).
- MESH :
- antagonistes et inhibiteurs : Transcriptase inverse du VIH.
- génétique : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- pharmacologie : Inhibiteurs de la transcriptase inverse, Thiocarbamates.
- synthèse chimique : Inhibiteurs de la transcriptase inverse, Thiocarbamates.
- Liaison aux protéines, Modèles moléculaires, Mutation faux-sens, Relation structure-activité, Simulation numérique, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Computer Simulation, HIV Reverse Transcriptase (antagonists & inhibitors), HIV-1 (drug effects), HIV-1 (genetics), Models, Molecular, Mutation, Missense, Protein Binding, Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship, Thiocarbamates (chemical synthesis), Thiocarbamates (pharmacology).
- MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Reverse Transcriptase Inhibitors, Thiocarbamates.
- drug effects : HIV-1.
- genetics : HIV-1.
- chemical , pharmacology : Reverse Transcriptase Inhibitors, Thiocarbamates.
- Computer Simulation, Models, Molecular, Mutation, Missense, Protein Binding, Structure-Activity Relationship.
Abstract
The structure-activity relationships (SARs) of acylthiocarbamates (ATCs), a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors, have been expanded. Sixty-six new analogues were prepared by parallel solution-phase synthesis. In general, the potency of new ATCs was better than that of the first series and O-[2-phthalimidoethyl] 4-chlorophenyl(3-nitrobenzoyl) thiocarbamate turned out to be the most potent ATC so far synthesized (EC(50)=1.5nM). Several ATCs were active at micromolar concentrations against HIV-1 strains carrying the RT Y181C mutation and one of them was also moderately active against the K103R variant. Docking simulations were carried out to rationalize the most relevant SARs.
DOI: 10.1016/j.ejmech.2008.10.032
PubMed: 19058881
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pubmed:19058881Le document en format XML
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(Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The structure-activity relationships (SARs) of acylthiocarbamates (ATCs), a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors, have been expanded. Sixty-six new analogues were prepared by parallel solution-phase synthesis. In general, the potency of new ATCs was better than that of the first series and O-[2-phthalimidoethyl] 4-chlorophenyl(3-nitrobenzoyl) thiocarbamate turned out to be the most potent ATC so far synthesized (EC(50)=1.5nM). Several ATCs were active at micromolar concentrations against HIV-1 strains carrying the RT Y181C mutation and one of them was also moderately active against the K103R variant. Docking simulations were carried out to rationalize the most relevant SARs.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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