Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs.
Identifieur interne : 001848 ( Main/Exploration ); précédent : 001847; suivant : 001849Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs.
Auteurs : Dongyue Li [République populaire de Chine] ; Peng Zhan ; Huiqing Liu ; Christophe Pannecouque ; Jan Balzarini ; Erik De Clercq ; Xinyong LiuSource :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2013.
Descripteurs français
- KwdFr :
- Délavirdine (pharmacologie), Humains, Infections à VIH (traitement médicamenteux), Infections à VIH (virologie), Inhibiteurs de la transcriptase inverse (), Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Lignée cellulaire, Névirapine (pharmacologie), Pyridazines (), Pyridazines (pharmacologie), Pyridazines (synthèse chimique), Relation structure-activité, Transcriptase inverse du VIH (antagonistes et inhibiteurs), Transcriptase inverse du VIH (métabolisme), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (enzymologie).
- MESH :
- antagonistes et inhibiteurs : Transcriptase inverse du VIH.
- enzymologie : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : Transcriptase inverse du VIH.
- pharmacologie : Délavirdine, Inhibiteurs de la transcriptase inverse, Névirapine, Pyridazines.
- synthèse chimique : Inhibiteurs de la transcriptase inverse, Pyridazines.
- traitement médicamenteux : Infections à VIH.
- virologie : Infections à VIH.
- Humains, Inhibiteurs de la transcriptase inverse, Lignée cellulaire, Pyridazines, Relation structure-activité, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
English descriptors
- KwdEn :
- Cell Line, Delavirdine (pharmacology), HIV Infections (drug therapy), HIV Infections (virology), HIV Reverse Transcriptase (antagonists & inhibitors), HIV Reverse Transcriptase (metabolism), HIV-1 (drug effects), HIV-1 (enzymology), Humans, Nevirapine (pharmacology), Pyridazines (chemical synthesis), Pyridazines (chemistry), Pyridazines (pharmacology), Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship.
- MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Pyridazines, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Pyridazines, Reverse Transcriptase Inhibitors.
- chemical , metabolism : HIV Reverse Transcriptase.
- chemical , pharmacology : Delavirdine, Nevirapine, Pyridazines, Reverse Transcriptase Inhibitors.
- drug effects : HIV-1.
- drug therapy : HIV Infections.
- enzymology : HIV-1.
- virology : HIV Infections.
- Cell Line, Humans, Structure-Activity Relationship.
Abstract
In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human immunodeficiency virus type 1) activity. Most of the title compounds displayed excellent anti-HIV-1 activity at submicromolar concentrations ranging from 34 nM to 5.08 μM. The most promising compound 8g inhibited HIV-1 IIIB in MT-4 cells at a low EC50 value (0.034 μM), which was lower than the reference drug nevirapine and delavirdine. The structure activity relationships (SARs) were discussed and rationalized by docking simulations.
DOI: 10.1016/j.bmc.2012.12.049
PubMed: 23415090
Affiliations:
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Humaine de type 1)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human immunodeficiency virus type 1) activity. Most of the title compounds displayed excellent anti-HIV-1 activity at submicromolar concentrations ranging from 34 nM to 5.08 μM. The most promising compound 8g inhibited HIV-1 IIIB in MT-4 cells at a low EC50 value (0.034 μM), which was lower than the reference drug nevirapine and delavirdine. The structure activity relationships (SARs) were discussed and rationalized by docking simulations.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name><name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name><name sortKey="Liu, Huiqing" sort="Liu, Huiqing" uniqKey="Liu H" first="Huiqing" last="Liu">Huiqing Liu</name><name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name><name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name><name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Li, Dongyue" sort="Li, Dongyue" uniqKey="Li D" first="Dongyue" last="Li">Dongyue Li</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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