Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.
Identifieur interne : 002F82 ( Main/Exploration ); précédent : 002F81; suivant : 002F83Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.
Auteurs : Sara Cesarini [Italie] ; Andrea Spallarossa ; Angelo Ranise ; Olga Bruno ; Paolo La Colla ; Barbara Secci ; Gabriella Collu ; Roberta LoddoSource :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2008.
Descripteurs français
- KwdFr :
- Inhibiteurs de la transcriptase inverse (), Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Modèles moléculaires, Nucléosides (), Relation structure-activité, Structure moléculaire, Thiocarbamates (), Thiocarbamates (pharmacologie), Thiocarbamates (synthèse chimique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (enzymologie).
- MESH :
- enzymologie : 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.
- Inhibiteurs de la transcriptase inverse, Modèles moléculaires, Nucléosides, Relation structure-activité, Structure moléculaire, Thiocarbamates, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- HIV-1 (drug effects), HIV-1 (enzymology), Models, Molecular, Molecular Structure, Nucleosides (chemistry), Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship, Thiocarbamates (chemical synthesis), Thiocarbamates (chemistry), Thiocarbamates (pharmacology).
- MESH :
- chemical , chemical synthesis : Reverse Transcriptase Inhibitors, Thiocarbamates.
- chemical , chemistry : Nucleosides, Reverse Transcriptase Inhibitors, Thiocarbamates.
- drug effects : HIV-1.
- enzymology : HIV-1.
- chemical , pharmacology : Reverse Transcriptase Inhibitors, Thiocarbamates.
- Models, Molecular, Molecular Structure, Structure-Activity Relationship.
Abstract
To acquire further insight into the structure-activity relationship (SAR) of the thiocarbamates (TCs) described in the preceding work, 57 analogues of the lead compound O-(2-phenylethyl)-N-phenylthiocarbamate I were prepared by parallel solution-phase synthesis. We varied the 2-phenylethyl moiety (mono-substitution on the phenyl ring and modification of the ethyl linker), keeping constant the N-phenyl ring substitutions which have given the best results in the previous series. Most of the new TCs inhibited wild-type HIV-1 at micro- and nanomolar concentrations in MT-4 cell-based assays. Some TCs were also active at micromolar concentrations against the Y181C and/or K103N/Y181C resistant mutants. The SARs were rationalized by docking simulations.
DOI: 10.1016/j.bmc.2007.12.046
PubMed: 18226533
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001C28
- to stream PubMed, to step Curation: 001C28
- to stream PubMed, to step Checkpoint: 001981
- to stream Ncbi, to step Merge: 001B64
- to stream Ncbi, to step Curation: 001B64
- to stream Ncbi, to step Checkpoint: 001B64
- to stream Main, to step Merge: 003047
- to stream Main, to step Curation: 002F82
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.</title><author><name sortKey="Cesarini, Sara" sort="Cesarini, Sara" uniqKey="Cesarini S" first="Sara" last="Cesarini">Sara Cesarini</name><affiliation wicri:level="1"><nlm:affiliation>Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy. sara.cesarini@unige.it</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova</wicri:regionArea><wicri:noRegion>I-16132 Genova</wicri:noRegion></affiliation></author><author><name sortKey="Spallarossa, Andrea" sort="Spallarossa, Andrea" uniqKey="Spallarossa A" first="Andrea" last="Spallarossa">Andrea Spallarossa</name></author><author><name sortKey="Ranise, Angelo" sort="Ranise, Angelo" uniqKey="Ranise A" first="Angelo" last="Ranise">Angelo Ranise</name></author><author><name sortKey="Bruno, Olga" sort="Bruno, Olga" uniqKey="Bruno O" first="Olga" last="Bruno">Olga Bruno</name></author><author><name sortKey="La Colla, Paolo" sort="La Colla, Paolo" uniqKey="La Colla P" first="Paolo" last="La Colla">Paolo La Colla</name></author><author><name sortKey="Secci, Barbara" sort="Secci, Barbara" uniqKey="Secci B" first="Barbara" last="Secci">Barbara Secci</name></author><author><name sortKey="Collu, Gabriella" sort="Collu, Gabriella" uniqKey="Collu G" first="Gabriella" last="Collu">Gabriella Collu</name></author><author><name sortKey="Loddo, Roberta" sort="Loddo, Roberta" uniqKey="Loddo R" first="Roberta" last="Loddo">Roberta Loddo</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18226533</idno><idno type="pmid">18226533</idno><idno type="doi">10.1016/j.bmc.2007.12.046</idno><idno type="wicri:Area/PubMed/Corpus">001C28</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001C28</idno><idno type="wicri:Area/PubMed/Curation">001C28</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001C28</idno><idno type="wicri:Area/PubMed/Checkpoint">001981</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001981</idno><idno type="wicri:Area/Ncbi/Merge">001B64</idno><idno type="wicri:Area/Ncbi/Curation">001B64</idno><idno type="wicri:Area/Ncbi/Checkpoint">001B64</idno><idno type="wicri:Area/Main/Merge">003047</idno><idno type="wicri:Area/Main/Curation">002F82</idno><idno type="wicri:Area/Main/Exploration">002F82</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.</title><author><name sortKey="Cesarini, Sara" sort="Cesarini, Sara" uniqKey="Cesarini S" first="Sara" last="Cesarini">Sara Cesarini</name><affiliation wicri:level="1"><nlm:affiliation>Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy. sara.cesarini@unige.it</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova</wicri:regionArea><wicri:noRegion>I-16132 Genova</wicri:noRegion></affiliation></author><author><name sortKey="Spallarossa, Andrea" sort="Spallarossa, Andrea" uniqKey="Spallarossa A" first="Andrea" last="Spallarossa">Andrea Spallarossa</name></author><author><name sortKey="Ranise, Angelo" sort="Ranise, Angelo" uniqKey="Ranise A" first="Angelo" last="Ranise">Angelo Ranise</name></author><author><name sortKey="Bruno, Olga" sort="Bruno, Olga" uniqKey="Bruno O" first="Olga" last="Bruno">Olga Bruno</name></author><author><name sortKey="La Colla, Paolo" sort="La Colla, Paolo" uniqKey="La Colla P" first="Paolo" last="La Colla">Paolo La Colla</name></author><author><name sortKey="Secci, Barbara" sort="Secci, Barbara" uniqKey="Secci B" first="Barbara" last="Secci">Barbara Secci</name></author><author><name sortKey="Collu, Gabriella" sort="Collu, Gabriella" uniqKey="Collu G" first="Gabriella" last="Collu">Gabriella Collu</name></author><author><name sortKey="Loddo, Roberta" sort="Loddo, Roberta" uniqKey="Loddo R" first="Roberta" last="Loddo">Roberta Loddo</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry</title><idno type="eISSN">1464-3391</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>HIV-1 (drug effects)</term><term>HIV-1 (enzymology)</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Nucleosides (chemistry)</term><term>Reverse Transcriptase Inhibitors (chemical synthesis)</term><term>Reverse Transcriptase Inhibitors (chemistry)</term><term>Reverse Transcriptase Inhibitors (pharmacology)</term><term>Structure-Activity Relationship</term><term>Thiocarbamates (chemical synthesis)</term><term>Thiocarbamates (chemistry)</term><term>Thiocarbamates (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse ()</term><term>Inhibiteurs de la transcriptase inverse (pharmacologie)</term><term>Inhibiteurs de la transcriptase inverse (synthèse chimique)</term><term>Modèles moléculaires</term><term>Nucléosides ()</term><term>Relation structure-activité</term><term>Structure moléculaire</term><term>Thiocarbamates ()</term><term>Thiocarbamates (pharmacologie)</term><term>Thiocarbamates (synthèse chimique)</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Reverse Transcriptase Inhibitors</term><term>Thiocarbamates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Nucleosides</term><term>Reverse Transcriptase Inhibitors</term><term>Thiocarbamates</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>HIV-1</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse</term><term>Thiocarbamates</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Reverse Transcriptase Inhibitors</term><term>Thiocarbamates</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse</term><term>Thiocarbamates</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Models, Molecular</term><term>Molecular Structure</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse</term><term>Modèles moléculaires</term><term>Nucléosides</term><term>Relation structure-activité</term><term>Structure moléculaire</term><term>Thiocarbamates</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To acquire further insight into the structure-activity relationship (SAR) of the thiocarbamates (TCs) described in the preceding work, 57 analogues of the lead compound O-(2-phenylethyl)-N-phenylthiocarbamate I were prepared by parallel solution-phase synthesis. We varied the 2-phenylethyl moiety (mono-substitution on the phenyl ring and modification of the ethyl linker), keeping constant the N-phenyl ring substitutions which have given the best results in the previous series. Most of the new TCs inhibited wild-type HIV-1 at micro- and nanomolar concentrations in MT-4 cell-based assays. Some TCs were also active at micromolar concentrations against the Y181C and/or K103N/Y181C resistant mutants. The SARs were rationalized by docking simulations.</div></front></TEI><affiliations><list><country><li>Italie</li></country></list><tree><noCountry><name sortKey="Bruno, Olga" sort="Bruno, Olga" uniqKey="Bruno O" first="Olga" last="Bruno">Olga Bruno</name><name sortKey="Collu, Gabriella" sort="Collu, Gabriella" uniqKey="Collu G" first="Gabriella" last="Collu">Gabriella Collu</name><name sortKey="La Colla, Paolo" sort="La Colla, Paolo" uniqKey="La Colla P" first="Paolo" last="La Colla">Paolo La Colla</name><name sortKey="Loddo, Roberta" sort="Loddo, Roberta" uniqKey="Loddo R" first="Roberta" last="Loddo">Roberta Loddo</name><name sortKey="Ranise, Angelo" sort="Ranise, Angelo" uniqKey="Ranise A" first="Angelo" last="Ranise">Angelo Ranise</name><name sortKey="Secci, Barbara" sort="Secci, Barbara" uniqKey="Secci B" first="Barbara" last="Secci">Barbara Secci</name><name sortKey="Spallarossa, Andrea" sort="Spallarossa, Andrea" uniqKey="Spallarossa A" first="Andrea" last="Spallarossa">Andrea Spallarossa</name></noCountry><country name="Italie"><noRegion><name sortKey="Cesarini, Sara" sort="Cesarini, Sara" uniqKey="Cesarini S" first="Sara" last="Cesarini">Sara Cesarini</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002F82 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002F82 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:18226533
|texte= Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:18226533" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |