3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone
Structure-based drug design using information from X-ray structures of ligands bound to the molecular chaperone Hsp90 has been used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides, several of which can make a hydrogen bond to Phe138 of the protein, affording incre...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2005-12, Vol.15 (23), p.5197-5201 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5201 |
|---|---|
| container_issue | 23 |
| container_start_page | 5197 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 15 |
| creator | Brough, Paul A. Barril, Xavier Beswick, Mandy Dymock, Brian W. Drysdale, Martin J. Wright, Lisa Grant, Kate Massey, Andrew Surgenor, Allan Workman, Paul |
| description | Structure-based drug design using information from X-ray structures of ligands bound to the molecular chaperone Hsp90 has been used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides, several of which can make a hydrogen bond to Phe138 of the protein, affording increased binding potency.
Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction. |
| doi_str_mv | 10.1016/j.bmcl.2005.08.091 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68707567</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X05010978</els_id><sourcerecordid>68707567</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-bc2cade5cfad56274d8463ecc8568cd681fb7f9c995ff2f5d94d2d7cc33282c3</originalsourceid><addsrcrecordid>eNp90EGL1TAQwPEgivt29Qt4kF6UFUxN0jRNwYss6goLetiDt5BOJjaPtqlJn2z99PbxHuzN01x-Mwx_Ql5xVnLG1Yd92Y0wlIKxumS6ZC1_QnZcKkkryeqnZMdaxahu5c8LcpnznjEumZTPyQVXglcNVzvyq6LXNYV-iClS8V5SF_rVpfiwzj1O6_CO_liT_RsHpJKCTV18sGNwmAubizD1oQtLTLmIvlh6LG7z3LJi3DgcBpsK6O2MKU74gjzzdsj48jyvyP2Xz_c3t_Tu-9dvN5_uKFRaLrQDAdZhDd66WolGOi1VhQC6Vhqc0tx3jW-hbWvvha9dK51wDUBVCS2guiJvT2fnFH8fMC9mDBlwGOyE8ZCN0g1ratVsUJwgpJhzQm_mFEabVsOZOdY1e3Osa451DdNmq7stvT5fP3QjuseVc84NvDkDm8EOPtkJQn50jWCtZEf38eRwS_EnYDIZAk6ALiSExbgY_vfHP1_fmQ4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68707567</pqid></control><display><type>article</type><title>3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Brough, Paul A. ; Barril, Xavier ; Beswick, Mandy ; Dymock, Brian W. ; Drysdale, Martin J. ; Wright, Lisa ; Grant, Kate ; Massey, Andrew ; Surgenor, Allan ; Workman, Paul</creator><creatorcontrib>Brough, Paul A. ; Barril, Xavier ; Beswick, Mandy ; Dymock, Brian W. ; Drysdale, Martin J. ; Wright, Lisa ; Grant, Kate ; Massey, Andrew ; Surgenor, Allan ; Workman, Paul</creatorcontrib><description>Structure-based drug design using information from X-ray structures of ligands bound to the molecular chaperone Hsp90 has been used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides, several of which can make a hydrogen bond to Phe138 of the protein, affording increased binding potency.
Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2005.08.091</identifier><identifier>PMID: 16213716</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Amides - chemistry ; Amides - pharmacology ; Antineoplastic agents ; Biological and medical sciences ; Cancer ; Crystallography, X-Ray ; Drug Design ; General aspects ; Hsp90 ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; Humans ; Medical sciences ; Molecular Structure ; Oxamic Acid - chemistry ; Pharmacology. Drug treatments ; Pyrazole ; Pyrazoles - chemistry ; Pyrazoles - pharmacology ; Structure-based drug design ; X-ray crystallography</subject><ispartof>Bioorganic & medicinal chemistry letters, 2005-12, Vol.15 (23), p.5197-5201</ispartof><rights>2005 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-bc2cade5cfad56274d8463ecc8568cd681fb7f9c995ff2f5d94d2d7cc33282c3</citedby><cites>FETCH-LOGICAL-c384t-bc2cade5cfad56274d8463ecc8568cd681fb7f9c995ff2f5d94d2d7cc33282c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2005.08.091$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17209406$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16213716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brough, Paul A.</creatorcontrib><creatorcontrib>Barril, Xavier</creatorcontrib><creatorcontrib>Beswick, Mandy</creatorcontrib><creatorcontrib>Dymock, Brian W.</creatorcontrib><creatorcontrib>Drysdale, Martin J.</creatorcontrib><creatorcontrib>Wright, Lisa</creatorcontrib><creatorcontrib>Grant, Kate</creatorcontrib><creatorcontrib>Massey, Andrew</creatorcontrib><creatorcontrib>Surgenor, Allan</creatorcontrib><creatorcontrib>Workman, Paul</creatorcontrib><title>3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Structure-based drug design using information from X-ray structures of ligands bound to the molecular chaperone Hsp90 has been used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides, several of which can make a hydrogen bond to Phe138 of the protein, affording increased binding potency.
Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.</description><subject>Amides - chemistry</subject><subject>Amides - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Crystallography, X-Ray</subject><subject>Drug Design</subject><subject>General aspects</subject><subject>Hsp90</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Oxamic Acid - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrazole</subject><subject>Pyrazoles - chemistry</subject><subject>Pyrazoles - pharmacology</subject><subject>Structure-based drug design</subject><subject>X-ray crystallography</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EGL1TAQwPEgivt29Qt4kF6UFUxN0jRNwYss6goLetiDt5BOJjaPtqlJn2z99PbxHuzN01x-Mwx_Ql5xVnLG1Yd92Y0wlIKxumS6ZC1_QnZcKkkryeqnZMdaxahu5c8LcpnznjEumZTPyQVXglcNVzvyq6LXNYV-iClS8V5SF_rVpfiwzj1O6_CO_liT_RsHpJKCTV18sGNwmAubizD1oQtLTLmIvlh6LG7z3LJi3DgcBpsK6O2MKU74gjzzdsj48jyvyP2Xz_c3t_Tu-9dvN5_uKFRaLrQDAdZhDd66WolGOi1VhQC6Vhqc0tx3jW-hbWvvha9dK51wDUBVCS2guiJvT2fnFH8fMC9mDBlwGOyE8ZCN0g1ratVsUJwgpJhzQm_mFEabVsOZOdY1e3Osa451DdNmq7stvT5fP3QjuseVc84NvDkDm8EOPtkJQn50jWCtZEf38eRwS_EnYDIZAk6ALiSExbgY_vfHP1_fmQ4</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Brough, Paul A.</creator><creator>Barril, Xavier</creator><creator>Beswick, Mandy</creator><creator>Dymock, Brian W.</creator><creator>Drysdale, Martin J.</creator><creator>Wright, Lisa</creator><creator>Grant, Kate</creator><creator>Massey, Andrew</creator><creator>Surgenor, Allan</creator><creator>Workman, Paul</creator><general>Elsevier Ltd</general><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>20051201</creationdate><title>3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone</title><author>Brough, Paul A. ; Barril, Xavier ; Beswick, Mandy ; Dymock, Brian W. ; Drysdale, Martin J. ; Wright, Lisa ; Grant, Kate ; Massey, Andrew ; Surgenor, Allan ; Workman, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-bc2cade5cfad56274d8463ecc8568cd681fb7f9c995ff2f5d94d2d7cc33282c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amides - chemistry</topic><topic>Amides - pharmacology</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Crystallography, X-Ray</topic><topic>Drug Design</topic><topic>General aspects</topic><topic>Hsp90</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>Oxamic Acid - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrazole</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrazoles - pharmacology</topic><topic>Structure-based drug design</topic><topic>X-ray crystallography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brough, Paul A.</creatorcontrib><creatorcontrib>Barril, Xavier</creatorcontrib><creatorcontrib>Beswick, Mandy</creatorcontrib><creatorcontrib>Dymock, Brian W.</creatorcontrib><creatorcontrib>Drysdale, Martin J.</creatorcontrib><creatorcontrib>Wright, Lisa</creatorcontrib><creatorcontrib>Grant, Kate</creatorcontrib><creatorcontrib>Massey, Andrew</creatorcontrib><creatorcontrib>Surgenor, Allan</creatorcontrib><creatorcontrib>Workman, Paul</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>Brough, Paul A.</au><au>Barril, Xavier</au><au>Beswick, Mandy</au><au>Dymock, Brian W.</au><au>Drysdale, Martin J.</au><au>Wright, Lisa</au><au>Grant, Kate</au><au>Massey, Andrew</au><au>Surgenor, Allan</au><au>Workman, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>15</volume><issue>23</issue><spage>5197</spage><epage>5201</epage><pages>5197-5201</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Structure-based drug design using information from X-ray structures of ligands bound to the molecular chaperone Hsp90 has been used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides, several of which can make a hydrogen bond to Phe138 of the protein, affording increased binding potency.
Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16213716</pmid><doi>10.1016/j.bmcl.2005.08.091</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2005-12, Vol.15 (23), p.5197-5201 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68707567 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Amides - chemistry Amides - pharmacology Antineoplastic agents Biological and medical sciences Cancer Crystallography, X-Ray Drug Design General aspects Hsp90 HSP90 Heat-Shock Proteins - antagonists & inhibitors Humans Medical sciences Molecular Structure Oxamic Acid - chemistry Pharmacology. Drug treatments Pyrazole Pyrazoles - chemistry Pyrazoles - pharmacology Structure-based drug design X-ray crystallography |
| title | 3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T18%3A27%3A49IST&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=3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides%20as%20inhibitors%20of%20the%20Hsp90%20molecular%20chaperone&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Brough,%20Paul%20A.&rft.date=2005-12-01&rft.volume=15&rft.issue=23&rft.spage=5197&rft.epage=5201&rft.pages=5197-5201&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2005.08.091&rft_dat=%3Cproquest_cross%3E68707567%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=68707567&rft_id=info:pmid/16213716&rft_els_id=S0960894X05010978&rfr_iscdi=true |