From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs
A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed.
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-09, Vol.19 (18), p.5429-5432 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5432 |
|---|---|
| container_issue | 18 |
| container_start_page | 5429 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 19 |
| creator | HANESSIAN, Stephen THERRIEN, Eric JIANBIN ZHANG VAN OTTERLO, Willem YAFENG XUE GUSTAFSSON, David NILSSON, Ingemar FJELLSTRÖM, Ola |
| description | A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed. |
| doi_str_mv | 10.1016/j.bmcl.2009.07.107 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_734016814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>734016814</sourcerecordid><originalsourceid>FETCH-LOGICAL-c247t-74169f3c200a6e05e66ca782332991c5c8c27a94a6773d4548d5c34e344f4b4c3</originalsourceid><addsrcrecordid>eNpFkE1r3DAQhkVpaLZp_0APRZeSkzf6GEtWbyUkaSCQPaTQm5AluavFtraSfNj--spkaU8D7zzvwDwIfaJkSwkVN4dtP9lxywhRWyJrJt-gDQUBDQfSvkUbogRpOgU_L9H7nA-EUCAA79AlVUJCp-QG_blPccKzKUsyIz6m6BZbMi4RG7sPa-bS8mtdlFhOR5-_4l0sfi647GuzDzMO8z70ocSUcW-ydzjOeMdudhy7sD-5FI-nFFzDmjh7bGPyeIolDPkDuhjMmP3H87xCP-7vXm6_N0_PD4-3354ay0CWRgIVauC2vmmEJ60XwhrZMc6ZUtS2trNMGgVGSMkdtNC51nLwHGCAHiy_Qtevd-sTvxefi55Ctn4czezjkrWstqjoKFSSvZI2xZyTH_Qxhcmkk6ZEr8r1Qa_K9apcE1kzWUufz-eXfvLuf-XsuAJfzoDJ1oxDMrMN-R_HqCIgpeB_AQxqi5E</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>734016814</pqid></control><display><type>article</type><title>From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>HANESSIAN, Stephen ; THERRIEN, Eric ; JIANBIN ZHANG ; VAN OTTERLO, Willem ; YAFENG XUE ; GUSTAFSSON, David ; NILSSON, Ingemar ; FJELLSTRÖM, Ola</creator><creatorcontrib>HANESSIAN, Stephen ; THERRIEN, Eric ; JIANBIN ZHANG ; VAN OTTERLO, Willem ; YAFENG XUE ; GUSTAFSSON, David ; NILSSON, Ingemar ; FJELLSTRÖM, Ola</creatorcontrib><description>A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.07.107</identifier><identifier>PMID: 19674897</identifier><language>eng</language><publisher>Amsterdam: Elsevier</publisher><subject>Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Cattle ; Crystallography, X-Ray ; Humans ; Medical sciences ; Models, Molecular ; Pharmacology. Drug treatments ; Protein Binding ; Pyridones - chemical synthesis ; Pyridones - chemistry ; Pyridones - pharmacology ; Serine Proteinase Inhibitors - chemical synthesis ; Serine Proteinase Inhibitors - chemistry ; Serine Proteinase Inhibitors - pharmacology ; Thrombin - antagonists & inhibitors ; Thrombin - chemistry ; Thrombin - metabolism ; Trypsin - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-09, Vol.19 (18), p.5429-5432</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c247t-74169f3c200a6e05e66ca782332991c5c8c27a94a6773d4548d5c34e344f4b4c3</citedby><cites>FETCH-LOGICAL-c247t-74169f3c200a6e05e66ca782332991c5c8c27a94a6773d4548d5c34e344f4b4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21904776$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19674897$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HANESSIAN, Stephen</creatorcontrib><creatorcontrib>THERRIEN, Eric</creatorcontrib><creatorcontrib>JIANBIN ZHANG</creatorcontrib><creatorcontrib>VAN OTTERLO, Willem</creatorcontrib><creatorcontrib>YAFENG XUE</creatorcontrib><creatorcontrib>GUSTAFSSON, David</creatorcontrib><creatorcontrib>NILSSON, Ingemar</creatorcontrib><creatorcontrib>FJELLSTRÖM, Ola</creatorcontrib><title>From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cattle</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding</subject><subject>Pyridones - chemical synthesis</subject><subject>Pyridones - chemistry</subject><subject>Pyridones - pharmacology</subject><subject>Serine Proteinase Inhibitors - chemical synthesis</subject><subject>Serine Proteinase Inhibitors - chemistry</subject><subject>Serine Proteinase Inhibitors - pharmacology</subject><subject>Thrombin - antagonists & inhibitors</subject><subject>Thrombin - chemistry</subject><subject>Thrombin - metabolism</subject><subject>Trypsin - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1r3DAQhkVpaLZp_0APRZeSkzf6GEtWbyUkaSCQPaTQm5AluavFtraSfNj--spkaU8D7zzvwDwIfaJkSwkVN4dtP9lxywhRWyJrJt-gDQUBDQfSvkUbogRpOgU_L9H7nA-EUCAA79AlVUJCp-QG_blPccKzKUsyIz6m6BZbMi4RG7sPa-bS8mtdlFhOR5-_4l0sfi647GuzDzMO8z70ocSUcW-ydzjOeMdudhy7sD-5FI-nFFzDmjh7bGPyeIolDPkDuhjMmP3H87xCP-7vXm6_N0_PD4-3354ay0CWRgIVauC2vmmEJ60XwhrZMc6ZUtS2trNMGgVGSMkdtNC51nLwHGCAHiy_Qtevd-sTvxefi55Ctn4czezjkrWstqjoKFSSvZI2xZyTH_Qxhcmkk6ZEr8r1Qa_K9apcE1kzWUufz-eXfvLuf-XsuAJfzoDJ1oxDMrMN-R_HqCIgpeB_AQxqi5E</recordid><startdate>20090915</startdate><enddate>20090915</enddate><creator>HANESSIAN, Stephen</creator><creator>THERRIEN, Eric</creator><creator>JIANBIN ZHANG</creator><creator>VAN OTTERLO, Willem</creator><creator>YAFENG XUE</creator><creator>GUSTAFSSON, David</creator><creator>NILSSON, Ingemar</creator><creator>FJELLSTRÖM, Ola</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090915</creationdate><title>From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs</title><author>HANESSIAN, Stephen ; THERRIEN, Eric ; JIANBIN ZHANG ; VAN OTTERLO, Willem ; YAFENG XUE ; GUSTAFSSON, David ; NILSSON, Ingemar ; FJELLSTRÖM, Ola</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c247t-74169f3c200a6e05e66ca782332991c5c8c27a94a6773d4548d5c34e344f4b4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cattle</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding</topic><topic>Pyridones - chemical synthesis</topic><topic>Pyridones - chemistry</topic><topic>Pyridones - pharmacology</topic><topic>Serine Proteinase Inhibitors - chemical synthesis</topic><topic>Serine Proteinase Inhibitors - chemistry</topic><topic>Serine Proteinase Inhibitors - pharmacology</topic><topic>Thrombin - antagonists & inhibitors</topic><topic>Thrombin - chemistry</topic><topic>Thrombin - metabolism</topic><topic>Trypsin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HANESSIAN, Stephen</creatorcontrib><creatorcontrib>THERRIEN, Eric</creatorcontrib><creatorcontrib>JIANBIN ZHANG</creatorcontrib><creatorcontrib>VAN OTTERLO, Willem</creatorcontrib><creatorcontrib>YAFENG XUE</creatorcontrib><creatorcontrib>GUSTAFSSON, David</creatorcontrib><creatorcontrib>NILSSON, Ingemar</creatorcontrib><creatorcontrib>FJELLSTRÖM, Ola</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HANESSIAN, Stephen</au><au>THERRIEN, Eric</au><au>JIANBIN ZHANG</au><au>VAN OTTERLO, Willem</au><au>YAFENG XUE</au><au>GUSTAFSSON, David</au><au>NILSSON, Ingemar</au><au>FJELLSTRÖM, Ola</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009-09-15</date><risdate>2009</risdate><volume>19</volume><issue>18</issue><spage>5429</spage><epage>5432</epage><pages>5429-5432</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A series of dihydropyrid-2-ones was synthesized and tested for inhibitory activity against serine protease enzymes. Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>19674897</pmid><doi>10.1016/j.bmcl.2009.07.107</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-09, Vol.19 (18), p.5429-5432 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734016814 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Cattle Crystallography, X-Ray Humans Medical sciences Models, Molecular Pharmacology. Drug treatments Protein Binding Pyridones - chemical synthesis Pyridones - chemistry Pyridones - pharmacology Serine Proteinase Inhibitors - chemical synthesis Serine Proteinase Inhibitors - chemistry Serine Proteinase Inhibitors - pharmacology Thrombin - antagonists & inhibitors Thrombin - chemistry Thrombin - metabolism Trypsin - metabolism |
| title | From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T16%3A43%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=From%20natural%20products%20to%20achiral%20drug%20prototypes:%20Potent%20thrombin%20inhibitors%20based%20on%20P2/P3%20dihydropyrid-2-one%20core%20motifs&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=HANESSIAN,%20Stephen&rft.date=2009-09-15&rft.volume=19&rft.issue=18&rft.spage=5429&rft.epage=5432&rft.pages=5429-5432&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2009.07.107&rft_dat=%3Cproquest_cross%3E734016814%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=734016814&rft_id=info:pmid/19674897&rfr_iscdi=true |