Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.
Identifieur interne : 000B59 ( Main/Exploration ); précédent : 000B58; suivant : 000B60Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.
Auteurs : Ji Yu [République populaire de Chine] ; Xiaowei Guo [République populaire de Chine] ; Samuel Desta [République populaire de Chine] ; Shuo Zhang [République populaire de Chine] ; Jian Zhang [République populaire de Chine] ; Xiao Ding [République populaire de Chine] ; Xiaohong Liang [République populaire de Chine] ; Haiyong Jia [République populaire de Chine] ; Xinyong Liu [République populaire de Chine] ; Peng Zhan [République populaire de Chine]Source :
- Chemical biology & drug design [ 1747-0285 ] ; 2019.
Abstract
In continuation of our efforts toward the discovery of potent non-nucleoside HBV inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidines (HAPs) derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure-activity relationships (SARs) of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. This article is protected by copyright. All rights reserved.
DOI: 10.1111/cbdd.13512
PubMed: 30825248
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000927
- to stream PubMed, to step Curation: 000927
- to stream PubMed, to step Checkpoint: 000913
- to stream Ncbi, to step Merge: 003023
- to stream Ncbi, to step Curation: 003023
- to stream Ncbi, to step Checkpoint: 003023
- to stream Main, to step Merge: 000B60
- to stream Main, to step Curation: 000B59
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.</title><author><name sortKey="Yu, Ji" sort="Yu, Ji" uniqKey="Yu J" first="Ji" last="Yu">Ji Yu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Guo, Xiaowei" sort="Guo, Xiaowei" uniqKey="Guo X" first="Xiaowei" last="Guo">Xiaowei Guo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province</wicri:regionArea><wicri:noRegion>Shandong Province</wicri:noRegion></affiliation></author><author><name sortKey="Desta, Samuel" sort="Desta, Samuel" uniqKey="Desta S" first="Samuel" last="Desta">Samuel Desta</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Shuo" sort="Zhang, Shuo" uniqKey="Zhang S" first="Shuo" last="Zhang">Shuo Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Ding, Xiao" sort="Ding, Xiao" uniqKey="Ding X" first="Xiao" last="Ding">Xiao Ding</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Xiaohong" sort="Liang, Xiaohong" uniqKey="Liang X" first="Xiaohong" last="Liang">Xiaohong Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province</wicri:regionArea><wicri:noRegion>Shandong Province</wicri:noRegion></affiliation></author><author><name sortKey="Jia, Haiyong" sort="Jia, Haiyong" uniqKey="Jia H" first="Haiyong" last="Jia">Haiyong Jia</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmacy, Weifang Medical University, 261053, Weifang, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Pharmacy, Weifang Medical University, 261053, Weifang, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30825248</idno><idno type="pmid">30825248</idno><idno type="doi">10.1111/cbdd.13512</idno><idno type="wicri:Area/PubMed/Corpus">000927</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000927</idno><idno type="wicri:Area/PubMed/Curation">000927</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000927</idno><idno type="wicri:Area/PubMed/Checkpoint">000913</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000913</idno><idno type="wicri:Area/Ncbi/Merge">003023</idno><idno type="wicri:Area/Ncbi/Curation">003023</idno><idno type="wicri:Area/Ncbi/Checkpoint">003023</idno><idno type="wicri:Area/Main/Merge">000B60</idno><idno type="wicri:Area/Main/Curation">000B59</idno><idno type="wicri:Area/Main/Exploration">000B59</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.</title><author><name sortKey="Yu, Ji" sort="Yu, Ji" uniqKey="Yu J" first="Ji" last="Yu">Ji Yu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Guo, Xiaowei" sort="Guo, Xiaowei" uniqKey="Guo X" first="Xiaowei" last="Guo">Xiaowei Guo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province</wicri:regionArea><wicri:noRegion>Shandong Province</wicri:noRegion></affiliation></author><author><name sortKey="Desta, Samuel" sort="Desta, Samuel" uniqKey="Desta S" first="Samuel" last="Desta">Samuel Desta</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Shuo" sort="Zhang, Shuo" uniqKey="Zhang S" first="Shuo" last="Zhang">Shuo Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Ding, Xiao" sort="Ding, Xiao" uniqKey="Ding X" first="Xiao" last="Ding">Xiao Ding</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Xiaohong" sort="Liang, Xiaohong" uniqKey="Liang X" first="Xiaohong" last="Liang">Xiaohong Liang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province</wicri:regionArea><wicri:noRegion>Shandong Province</wicri:noRegion></affiliation></author><author><name sortKey="Jia, Haiyong" sort="Jia, Haiyong" uniqKey="Jia H" first="Haiyong" last="Jia">Haiyong Jia</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmacy, Weifang Medical University, 261053, Weifang, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Pharmacy, Weifang Medical University, 261053, Weifang, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author></analytic><series><title level="j">Chemical biology & drug design</title><idno type="eISSN">1747-0285</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In continuation of our efforts toward the discovery of potent non-nucleoside HBV inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidines (HAPs) derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC<sub>50</sub> = 0.35 ± 0.04 μM). The preliminary structure-activity relationships (SARs) of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. This article is protected by copyright. All rights reserved.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yu, Ji" sort="Yu, Ji" uniqKey="Yu J" first="Ji" last="Yu">Ji Yu</name></noRegion><name sortKey="Desta, Samuel" sort="Desta, Samuel" uniqKey="Desta S" first="Samuel" last="Desta">Samuel Desta</name><name sortKey="Ding, Xiao" sort="Ding, Xiao" uniqKey="Ding X" first="Xiao" last="Ding">Xiao Ding</name><name sortKey="Guo, Xiaowei" sort="Guo, Xiaowei" uniqKey="Guo X" first="Xiaowei" last="Guo">Xiaowei Guo</name><name sortKey="Jia, Haiyong" sort="Jia, Haiyong" uniqKey="Jia H" first="Haiyong" last="Jia">Haiyong Jia</name><name sortKey="Liang, Xiaohong" sort="Liang, Xiaohong" uniqKey="Liang X" first="Xiaohong" last="Liang">Xiaohong Liang</name><name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name><name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><name sortKey="Zhang, Shuo" sort="Zhang, Shuo" uniqKey="Zhang S" first="Shuo" last="Zhang">Shuo Zhang</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 000B59 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000B59 | 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:30825248
|texte= Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:30825248" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |