Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.
Identifieur interne : 001003 ( Main/Exploration ); précédent : 001002; suivant : 001004Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.
Auteurs : Jacob J. Swidorski [États-Unis] ; Zheng Liu [États-Unis] ; Zhiwei Yin [États-Unis] ; Tao Wang [États-Unis] ; David J. Carini [États-Unis] ; Sandhya Rahematpura [États-Unis] ; Ming Zheng [États-Unis] ; Kim Johnson [États-Unis] ; Sharon Zhang [États-Unis] ; Pin-Fang Lin [États-Unis] ; Dawn D. Parker [États-Unis] ; Wenying Li [États-Unis] ; Nicholas A. Meanwell [États-Unis] ; Lawrence G. Hamann [États-Unis] ; Alicia Regueiro-Ren [États-Unis]Source :
- Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2016.
Descripteurs français
- KwdFr :
- Attachement viral (), Benzamides (), Cellules HeLa, Composés aza (), Découverte de médicament, Humains, Indoles (), Infections à VIH (génétique), Infections à VIH (traitement médicamenteux), Inhibiteurs de fusion du VIH (), Inhibiteurs de fusion du VIH (pharmacologie), Inhibiteurs de fusion du VIH (synthèse chimique), Pipérazines (), Protéine d'enveloppe gp120 du VIH (antagonistes et inhibiteurs), Protéine d'enveloppe gp120 du VIH (génétique), Relation dose-effet des médicaments, Relation structure-activité, Réplication virale (), Structure moléculaire, Survie cellulaire (), Tétrahydroisoquinoléines (), Tétrahydroisoquinoléines (pharmacologie), Tétrahydroisoquinoléines (synthèse chimique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ().
- MESH :
- antagonistes et inhibiteurs : Protéine d'enveloppe gp120 du VIH.
- génétique : Infections à VIH, Protéine d'enveloppe gp120 du VIH.
- pharmacologie : Inhibiteurs de fusion du VIH, Tétrahydroisoquinoléines.
- synthèse chimique : Inhibiteurs de fusion du VIH, Tétrahydroisoquinoléines.
- traitement médicamenteux : Infections à VIH.
- Attachement viral, Benzamides, Cellules HeLa, Composés aza, Découverte de médicament, Humains, Indoles, Inhibiteurs de fusion du VIH, Pipérazines, Relation dose-effet des médicaments, Relation structure-activité, Réplication virale, Structure moléculaire, Survie cellulaire, Tétrahydroisoquinoléines, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Aza Compounds (chemistry), Benzamides (chemistry), Cell Survival (drug effects), Dose-Response Relationship, Drug, Drug Discovery, HIV Envelope Protein gp120 (antagonists & inhibitors), HIV Envelope Protein gp120 (genetics), HIV Fusion Inhibitors (chemical synthesis), HIV Fusion Inhibitors (chemistry), HIV Fusion Inhibitors (pharmacology), HIV Infections (drug therapy), HIV Infections (genetics), HIV-1 (drug effects), HeLa Cells, Humans, Indoles (chemistry), Molecular Structure, Piperazines (chemistry), Structure-Activity Relationship, Tetrahydroisoquinolines (chemical synthesis), Tetrahydroisoquinolines (chemistry), Tetrahydroisoquinolines (pharmacology), Virus Attachment (drug effects), Virus Replication (drug effects).
- MESH :
- chemical , antagonists & inhibitors : HIV Envelope Protein gp120.
- chemical , chemical synthesis : HIV Fusion Inhibitors, Tetrahydroisoquinolines.
- chemical , chemistry : Aza Compounds, Benzamides, HIV Fusion Inhibitors, Indoles, Piperazines, Tetrahydroisoquinolines.
- drug effects : Cell Survival, HIV-1, Virus Attachment, Virus Replication.
- drug therapy : HIV Infections.
- chemical , genetics : HIV Envelope Protein gp120, HIV Infections.
- chemical , pharmacology : HIV Fusion Inhibitors, Tetrahydroisoquinolines.
- Dose-Response Relationship, Drug, Drug Discovery, HeLa Cells, Humans, Molecular Structure, Structure-Activity Relationship.
Abstract
6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein.
DOI: 10.1016/j.bmcl.2015.11.009
PubMed: 26584882
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000D38
- to stream PubMed, to step Curation: 000D38
- to stream PubMed, to step Checkpoint: 000C37
- to stream Ncbi, to step Merge: 002B62
- to stream Ncbi, to step Curation: 002B62
- to stream Ncbi, to step Checkpoint: 002B62
- to stream Main, to step Merge: 001005
- to stream Main, to step Curation: 001003
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.</title><author><name sortKey="Swidorski, Jacob J" sort="Swidorski, Jacob J" uniqKey="Swidorski J" first="Jacob J" last="Swidorski">Jacob J. Swidorski</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Liu, Zheng" sort="Liu, Zheng" uniqKey="Liu Z" first="Zheng" last="Liu">Zheng Liu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Yin, Zhiwei" sort="Yin, Zhiwei" uniqKey="Yin Z" first="Zhiwei" last="Yin">Zhiwei Yin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Carini, David J" sort="Carini, David J" uniqKey="Carini D" first="David J" last="Carini">David J. Carini</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Rahematpura, Sandhya" sort="Rahematpura, Sandhya" uniqKey="Rahematpura S" first="Sandhya" last="Rahematpura">Sandhya Rahematpura</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Zheng, Ming" sort="Zheng, Ming" uniqKey="Zheng M" first="Ming" last="Zheng">Ming Zheng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Johnson, Kim" sort="Johnson, Kim" uniqKey="Johnson K" first="Kim" last="Johnson">Kim Johnson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Zhang, Sharon" sort="Zhang, Sharon" uniqKey="Zhang S" first="Sharon" last="Zhang">Sharon Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Lin, Pin Fang" sort="Lin, Pin Fang" uniqKey="Lin P" first="Pin-Fang" last="Lin">Pin-Fang Lin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Parker, Dawn D" sort="Parker, Dawn D" uniqKey="Parker D" first="Dawn D" last="Parker">Dawn D. Parker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Li, Wenying" sort="Li, Wenying" uniqKey="Li W" first="Wenying" last="Li">Wenying Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Meanwell, Nicholas A" sort="Meanwell, Nicholas A" uniqKey="Meanwell N" first="Nicholas A" last="Meanwell">Nicholas A. Meanwell</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Hamann, Lawrence G" sort="Hamann, Lawrence G" uniqKey="Hamann L" first="Lawrence G" last="Hamann">Lawrence G. Hamann</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Regueiro Ren, Alicia" sort="Regueiro Ren, Alicia" uniqKey="Regueiro Ren A" first="Alicia" last="Regueiro-Ren">Alicia Regueiro-Ren</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26584882</idno><idno type="pmid">26584882</idno><idno type="doi">10.1016/j.bmcl.2015.11.009</idno><idno type="wicri:Area/PubMed/Corpus">000D38</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D38</idno><idno type="wicri:Area/PubMed/Curation">000D38</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D38</idno><idno type="wicri:Area/PubMed/Checkpoint">000C37</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C37</idno><idno type="wicri:Area/Ncbi/Merge">002B62</idno><idno type="wicri:Area/Ncbi/Curation">002B62</idno><idno type="wicri:Area/Ncbi/Checkpoint">002B62</idno><idno type="wicri:Area/Main/Merge">001005</idno><idno type="wicri:Area/Main/Curation">001003</idno><idno type="wicri:Area/Main/Exploration">001003</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.</title><author><name sortKey="Swidorski, Jacob J" sort="Swidorski, Jacob J" uniqKey="Swidorski J" first="Jacob J" last="Swidorski">Jacob J. Swidorski</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Liu, Zheng" sort="Liu, Zheng" uniqKey="Liu Z" first="Zheng" last="Liu">Zheng Liu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Yin, Zhiwei" sort="Yin, Zhiwei" uniqKey="Yin Z" first="Zhiwei" last="Yin">Zhiwei Yin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Carini, David J" sort="Carini, David J" uniqKey="Carini D" first="David J" last="Carini">David J. Carini</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Rahematpura, Sandhya" sort="Rahematpura, Sandhya" uniqKey="Rahematpura S" first="Sandhya" last="Rahematpura">Sandhya Rahematpura</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Zheng, Ming" sort="Zheng, Ming" uniqKey="Zheng M" first="Ming" last="Zheng">Ming Zheng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Johnson, Kim" sort="Johnson, Kim" uniqKey="Johnson K" first="Kim" last="Johnson">Kim Johnson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Zhang, Sharon" sort="Zhang, Sharon" uniqKey="Zhang S" first="Sharon" last="Zhang">Sharon Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Lin, Pin Fang" sort="Lin, Pin Fang" uniqKey="Lin P" first="Pin-Fang" last="Lin">Pin-Fang Lin</name><affiliation wicri:level="2"><nlm:affiliation>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Parker, Dawn D" sort="Parker, Dawn D" uniqKey="Parker D" first="Dawn D" last="Parker">Dawn D. Parker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Li, Wenying" sort="Li, Wenying" uniqKey="Li W" first="Wenying" last="Li">Wenying Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Meanwell, Nicholas A" sort="Meanwell, Nicholas A" uniqKey="Meanwell N" first="Nicholas A" last="Meanwell">Nicholas A. Meanwell</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Hamann, Lawrence G" sort="Hamann, Lawrence G" uniqKey="Hamann L" first="Lawrence G" last="Hamann">Lawrence G. Hamann</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Regueiro Ren, Alicia" sort="Regueiro Ren, Alicia" uniqKey="Regueiro Ren A" first="Alicia" last="Regueiro-Ren">Alicia Regueiro-Ren</name><affiliation wicri:level="2"><nlm:affiliation>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author></analytic><series><title level="j">Bioorganic & medicinal chemistry letters</title><idno type="eISSN">1464-3405</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aza Compounds (chemistry)</term><term>Benzamides (chemistry)</term><term>Cell Survival (drug effects)</term><term>Dose-Response Relationship, Drug</term><term>Drug Discovery</term><term>HIV Envelope Protein gp120 (antagonists & inhibitors)</term><term>HIV Envelope Protein gp120 (genetics)</term><term>HIV Fusion Inhibitors (chemical synthesis)</term><term>HIV Fusion Inhibitors (chemistry)</term><term>HIV Fusion Inhibitors (pharmacology)</term><term>HIV Infections (drug therapy)</term><term>HIV Infections (genetics)</term><term>HIV-1 (drug effects)</term><term>HeLa Cells</term><term>Humans</term><term>Indoles (chemistry)</term><term>Molecular Structure</term><term>Piperazines (chemistry)</term><term>Structure-Activity Relationship</term><term>Tetrahydroisoquinolines (chemical synthesis)</term><term>Tetrahydroisoquinolines (chemistry)</term><term>Tetrahydroisoquinolines (pharmacology)</term><term>Virus Attachment (drug effects)</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Attachement viral ()</term><term>Benzamides ()</term><term>Cellules HeLa</term><term>Composés aza ()</term><term>Découverte de médicament</term><term>Humains</term><term>Indoles ()</term><term>Infections à VIH (génétique)</term><term>Infections à VIH (traitement médicamenteux)</term><term>Inhibiteurs de fusion du VIH ()</term><term>Inhibiteurs de fusion du VIH (pharmacologie)</term><term>Inhibiteurs de fusion du VIH (synthèse chimique)</term><term>Pipérazines ()</term><term>Protéine d'enveloppe gp120 du VIH (antagonistes et inhibiteurs)</term><term>Protéine d'enveloppe gp120 du VIH (génétique)</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Réplication virale ()</term><term>Structure moléculaire</term><term>Survie cellulaire ()</term><term>Tétrahydroisoquinoléines ()</term><term>Tétrahydroisoquinoléines (pharmacologie)</term><term>Tétrahydroisoquinoléines (synthèse chimique)</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>HIV Envelope Protein gp120</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>HIV Fusion Inhibitors</term><term>Tetrahydroisoquinolines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aza Compounds</term><term>Benzamides</term><term>HIV Fusion Inhibitors</term><term>Indoles</term><term>Piperazines</term><term>Tetrahydroisoquinolines</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéine d'enveloppe gp120 du VIH</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>HIV-1</term><term>Virus Attachment</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>HIV Infections</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HIV Envelope Protein gp120</term><term>HIV Infections</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Infections à VIH</term><term>Protéine d'enveloppe gp120 du VIH</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de fusion du VIH</term><term>Tétrahydroisoquinoléines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>HIV Fusion Inhibitors</term><term>Tetrahydroisoquinolines</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Inhibiteurs de fusion du VIH</term><term>Tétrahydroisoquinoléines</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à VIH</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term><term>Drug Discovery</term><term>HeLa Cells</term><term>Humans</term><term>Molecular Structure</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Attachement viral</term><term>Benzamides</term><term>Cellules HeLa</term><term>Composés aza</term><term>Découverte de médicament</term><term>Humains</term><term>Indoles</term><term>Inhibiteurs de fusion du VIH</term><term>Pipérazines</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Réplication virale</term><term>Structure moléculaire</term><term>Survie cellulaire</term><term>Tétrahydroisoquinoléines</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein. </div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li></region></list><tree><country name="États-Unis"><region name="Connecticut"><name sortKey="Swidorski, Jacob J" sort="Swidorski, Jacob J" uniqKey="Swidorski J" first="Jacob J" last="Swidorski">Jacob J. Swidorski</name></region><name sortKey="Carini, David J" sort="Carini, David J" uniqKey="Carini D" first="David J" last="Carini">David J. Carini</name><name sortKey="Hamann, Lawrence G" sort="Hamann, Lawrence G" uniqKey="Hamann L" first="Lawrence G" last="Hamann">Lawrence G. Hamann</name><name sortKey="Johnson, Kim" sort="Johnson, Kim" uniqKey="Johnson K" first="Kim" last="Johnson">Kim Johnson</name><name sortKey="Li, Wenying" sort="Li, Wenying" uniqKey="Li W" first="Wenying" last="Li">Wenying Li</name><name sortKey="Lin, Pin Fang" sort="Lin, Pin Fang" uniqKey="Lin P" first="Pin-Fang" last="Lin">Pin-Fang Lin</name><name sortKey="Liu, Zheng" sort="Liu, Zheng" uniqKey="Liu Z" first="Zheng" last="Liu">Zheng Liu</name><name sortKey="Meanwell, Nicholas A" sort="Meanwell, Nicholas A" uniqKey="Meanwell N" first="Nicholas A" last="Meanwell">Nicholas A. Meanwell</name><name sortKey="Parker, Dawn D" sort="Parker, Dawn D" uniqKey="Parker D" first="Dawn D" last="Parker">Dawn D. Parker</name><name sortKey="Rahematpura, Sandhya" sort="Rahematpura, Sandhya" uniqKey="Rahematpura S" first="Sandhya" last="Rahematpura">Sandhya Rahematpura</name><name sortKey="Regueiro Ren, Alicia" sort="Regueiro Ren, Alicia" uniqKey="Regueiro Ren A" first="Alicia" last="Regueiro-Ren">Alicia Regueiro-Ren</name><name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name><name sortKey="Yin, Zhiwei" sort="Yin, Zhiwei" uniqKey="Yin Z" first="Zhiwei" last="Yin">Zhiwei Yin</name><name sortKey="Zhang, Sharon" sort="Zhang, Sharon" uniqKey="Zhang S" first="Sharon" last="Zhang">Sharon Zhang</name><name sortKey="Zheng, Ming" sort="Zheng, Ming" uniqKey="Zheng M" first="Ming" last="Zheng">Ming Zheng</name></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 001003 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001003 | 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:26584882
|texte= Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26584882" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |