Pyrazolone based TGFbetaR1 kinase inhibitors
Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitor...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2010-01, Vol.20 (1), p.326-329 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 329 |
|---|---|
| container_issue | 1 |
| container_start_page | 326 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Guckian, Kevin Carter, Mary Beth Lin, Edward Yin-Shiang Choi, Michael Sun, Lihong Boriack-Sjodin, P Ann Chuaqui, Claudio Lane, Benjamin Cheung, Kam Ling, Leona Lee, Wen-Cherng |
| description | Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232. |
| doi_str_mv | 10.1016/j.bmcl.2009.10.108 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_733950168</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>733950168</sourcerecordid><originalsourceid>FETCH-LOGICAL-p558-7b940d8c7520c2c7967e4f726c8eaf92b366b9f9c86a4c4f7a56b3778c4638be3</originalsourceid><addsrcrecordid>eNo1j01Lw0AYhBdBbK3-AQ-SmxeT7ma_j1JsFQoVyT3sbt7g1ny5mxzqrzdoPc3wzDAwCN0RnBFMxPqY2dY1WY6xzn6ZukBLwgRLKcN8ga5jPGJMGGbsCi2I1rMVaoke307BfPdN30FiTYQqKXZbC6N5J8mn72aS-O7DWz_2Id6gy9o0EW7PukLF9rnYvKT7w-5187RPB85VKq1muFJO8hy73EktJLBa5sIpMLXOLRXC6lo7JQxzc2K4sFRK5ZigygJdoYe_2SH0XxPEsWx9dNA0poN-iqWkVPP5tJqb9-fmZFuoyiH41oRT-f-P_gCFuE-5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733950168</pqid></control><display><type>article</type><title>Pyrazolone based TGFbetaR1 kinase inhibitors</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Guckian, Kevin ; Carter, Mary Beth ; Lin, Edward Yin-Shiang ; Choi, Michael ; Sun, Lihong ; Boriack-Sjodin, P Ann ; Chuaqui, Claudio ; Lane, Benjamin ; Cheung, Kam ; Ling, Leona ; Lee, Wen-Cherng</creator><creatorcontrib>Guckian, Kevin ; Carter, Mary Beth ; Lin, Edward Yin-Shiang ; Choi, Michael ; Sun, Lihong ; Boriack-Sjodin, P Ann ; Chuaqui, Claudio ; Lane, Benjamin ; Cheung, Kam ; Ling, Leona ; Lee, Wen-Cherng</creatorcontrib><description>Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.</description><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.10.108</identifier><identifier>PMID: 19914068</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Binding Sites ; Crystallography, X-Ray ; Mice ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacokinetics ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Pyrazolones - chemical synthesis ; Pyrazolones - chemistry ; Pyrazolones - pharmacokinetics ; Rats ; Receptors, Transforming Growth Factor beta - antagonists & inhibitors ; Receptors, Transforming Growth Factor beta - metabolism ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2010-01, Vol.20 (1), p.326-329</ispartof><rights>Copyright 2009 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19914068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guckian, Kevin</creatorcontrib><creatorcontrib>Carter, Mary Beth</creatorcontrib><creatorcontrib>Lin, Edward Yin-Shiang</creatorcontrib><creatorcontrib>Choi, Michael</creatorcontrib><creatorcontrib>Sun, Lihong</creatorcontrib><creatorcontrib>Boriack-Sjodin, P Ann</creatorcontrib><creatorcontrib>Chuaqui, Claudio</creatorcontrib><creatorcontrib>Lane, Benjamin</creatorcontrib><creatorcontrib>Cheung, Kam</creatorcontrib><creatorcontrib>Ling, Leona</creatorcontrib><creatorcontrib>Lee, Wen-Cherng</creatorcontrib><title>Pyrazolone based TGFbetaR1 kinase inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Crystallography, X-Ray</subject><subject>Mice</subject><subject>Protein Kinase Inhibitors - chemical synthesis</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacokinetics</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Pyrazolones - chemical synthesis</subject><subject>Pyrazolones - chemistry</subject><subject>Pyrazolones - pharmacokinetics</subject><subject>Rats</subject><subject>Receptors, Transforming Growth Factor beta - antagonists & inhibitors</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j01Lw0AYhBdBbK3-AQ-SmxeT7ma_j1JsFQoVyT3sbt7g1ny5mxzqrzdoPc3wzDAwCN0RnBFMxPqY2dY1WY6xzn6ZukBLwgRLKcN8ga5jPGJMGGbsCi2I1rMVaoke307BfPdN30FiTYQqKXZbC6N5J8mn72aS-O7DWz_2Id6gy9o0EW7PukLF9rnYvKT7w-5187RPB85VKq1muFJO8hy73EktJLBa5sIpMLXOLRXC6lo7JQxzc2K4sFRK5ZigygJdoYe_2SH0XxPEsWx9dNA0poN-iqWkVPP5tJqb9-fmZFuoyiH41oRT-f-P_gCFuE-5</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Guckian, Kevin</creator><creator>Carter, Mary Beth</creator><creator>Lin, Edward Yin-Shiang</creator><creator>Choi, Michael</creator><creator>Sun, Lihong</creator><creator>Boriack-Sjodin, P Ann</creator><creator>Chuaqui, Claudio</creator><creator>Lane, Benjamin</creator><creator>Cheung, Kam</creator><creator>Ling, Leona</creator><creator>Lee, Wen-Cherng</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20100101</creationdate><title>Pyrazolone based TGFbetaR1 kinase inhibitors</title><author>Guckian, Kevin ; Carter, Mary Beth ; Lin, Edward Yin-Shiang ; Choi, Michael ; Sun, Lihong ; Boriack-Sjodin, P Ann ; Chuaqui, Claudio ; Lane, Benjamin ; Cheung, Kam ; Ling, Leona ; Lee, Wen-Cherng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p558-7b940d8c7520c2c7967e4f726c8eaf92b366b9f9c86a4c4f7a56b3778c4638be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Crystallography, X-Ray</topic><topic>Mice</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacokinetics</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Pyrazolones - chemical synthesis</topic><topic>Pyrazolones - chemistry</topic><topic>Pyrazolones - pharmacokinetics</topic><topic>Rats</topic><topic>Receptors, Transforming Growth Factor beta - antagonists & inhibitors</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guckian, Kevin</creatorcontrib><creatorcontrib>Carter, Mary Beth</creatorcontrib><creatorcontrib>Lin, Edward Yin-Shiang</creatorcontrib><creatorcontrib>Choi, Michael</creatorcontrib><creatorcontrib>Sun, Lihong</creatorcontrib><creatorcontrib>Boriack-Sjodin, P Ann</creatorcontrib><creatorcontrib>Chuaqui, Claudio</creatorcontrib><creatorcontrib>Lane, Benjamin</creatorcontrib><creatorcontrib>Cheung, Kam</creatorcontrib><creatorcontrib>Ling, Leona</creatorcontrib><creatorcontrib>Lee, Wen-Cherng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guckian, Kevin</au><au>Carter, Mary Beth</au><au>Lin, Edward Yin-Shiang</au><au>Choi, Michael</au><au>Sun, Lihong</au><au>Boriack-Sjodin, P Ann</au><au>Chuaqui, Claudio</au><au>Lane, Benjamin</au><au>Cheung, Kam</au><au>Ling, Leona</au><au>Lee, Wen-Cherng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyrazolone based TGFbetaR1 kinase inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>20</volume><issue>1</issue><spage>326</spage><epage>329</epage><pages>326-329</pages><eissn>1464-3405</eissn><abstract>Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.</abstract><cop>England</cop><pmid>19914068</pmid><doi>10.1016/j.bmcl.2009.10.108</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | EISSN: 1464-3405 |
| ispartof | Bioorganic & medicinal chemistry letters, 2010-01, Vol.20 (1), p.326-329 |
| issn | 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733950168 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Binding Sites Crystallography, X-Ray Mice Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Pyrazolones - chemical synthesis Pyrazolones - chemistry Pyrazolones - pharmacokinetics Rats Receptors, Transforming Growth Factor beta - antagonists & inhibitors Receptors, Transforming Growth Factor beta - metabolism Structure-Activity Relationship |
| title | Pyrazolone based TGFbetaR1 kinase inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T23%3A33%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pyrazolone%20based%20TGFbetaR1%20kinase%20inhibitors&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Guckian,%20Kevin&rft.date=2010-01-01&rft.volume=20&rft.issue=1&rft.spage=326&rft.epage=329&rft.pages=326-329&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2009.10.108&rft_dat=%3Cproquest_pubme%3E733950168%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733950168&rft_id=info:pmid/19914068&rfr_iscdi=true |