Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies
A series of pyrazole amides was synthesized and screened for JNK-1 inhibitory and anti-inflammatory activity. Docking study was also performed. Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inh...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2014-11, Vol.22 (21), p.6209-6219 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6219 |
|---|---|
| container_issue | 21 |
| container_start_page | 6209 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 22 |
| creator | Doma, Anuradha Kulkarni, Ravindra Palakodety, Radhakrishna Sastry, G. Narahari Sridhara, Janardhan Garlapati, Achaiah |
| description | A series of pyrazole amides was synthesized and screened for JNK-1 inhibitory and anti-inflammatory activity. Docking study was also performed.
Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10μM, in particular compounds 9c, 10a and 10d were found to be potent among all the compounds. |
| doi_str_mv | 10.1016/j.bmc.2014.08.028 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1635035350</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089614006154</els_id><sourcerecordid>1635035350</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-652d8295118d925d500b3a7c15a4f82fdcef2c17991041ef102d7ce4f33cb0623</originalsourceid><addsrcrecordid>eNqFkT1vFDEURS0EIpuEH0CDXNLM4GePvTZUURQCKCKIhNry2G8UL_Ox2J6VNr-eWW2ghOa-5txbvEPIa2A1MFDvNnU7-JozaGqma8b1M7KCRjWVEAaekxUzSldMG3VCTnPeMMZ4Y-AlOeGSKzDcrIj9tk_uceqRBkxx50rcYaYu0-1UcCw0jg-xjWVKmU4d9dWXeaRfq4JpiKPr6c8lM76nd_uxPGCOS3UM9O7iO81lDhHzOXnRuT7jq6d7Rn58vLq__FTd3F5_vry4qbzQqlRK8qC5kQA6GC6DZKwVbu1BuqbTvAseO-5hbQywBrADxsPaY9MJ4VumuDgjb4-72zT9mjEXO8Tsse_diNOcLSghmZCH-D_KjVFcS72gcER9mnJO2NltioNLewvMHhTYjV0U2IMCy7RdFCydN0_zcztg-Nv48_MF-HAEcPnHLmKy2UccPYaY0BcbpviP-d9tC5Xz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1629962858</pqid></control><display><type>article</type><title>Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Doma, Anuradha ; Kulkarni, Ravindra ; Palakodety, Radhakrishna ; Sastry, G. Narahari ; Sridhara, Janardhan ; Garlapati, Achaiah</creator><creatorcontrib>Doma, Anuradha ; Kulkarni, Ravindra ; Palakodety, Radhakrishna ; Sastry, G. Narahari ; Sridhara, Janardhan ; Garlapati, Achaiah</creatorcontrib><description>A series of pyrazole amides was synthesized and screened for JNK-1 inhibitory and anti-inflammatory activity. Docking study was also performed.
Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10μM, in particular compounds 9c, 10a and 10d were found to be potent among all the compounds.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2014.08.028</identifier><identifier>PMID: 25261929</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amides - chemistry ; Amides - pharmacology ; Amides - therapeutic use ; Animals ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Edema - drug therapy ; Humans ; IC50 ; Inflammation ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - chemistry ; JNK Mitogen-Activated Protein Kinases - metabolism ; JNK-1 ; Molecular Docking Simulation ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Pyrazoles ; Pyrazoles - chemistry ; Pyrazoles - pharmacology ; Pyrazoles - therapeutic use ; Rats ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2014-11, Vol.22 (21), p.6209-6219</ispartof><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-652d8295118d925d500b3a7c15a4f82fdcef2c17991041ef102d7ce4f33cb0623</citedby><cites>FETCH-LOGICAL-c386t-652d8295118d925d500b3a7c15a4f82fdcef2c17991041ef102d7ce4f33cb0623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2014.08.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25261929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Doma, Anuradha</creatorcontrib><creatorcontrib>Kulkarni, Ravindra</creatorcontrib><creatorcontrib>Palakodety, Radhakrishna</creatorcontrib><creatorcontrib>Sastry, G. Narahari</creatorcontrib><creatorcontrib>Sridhara, Janardhan</creatorcontrib><creatorcontrib>Garlapati, Achaiah</creatorcontrib><title>Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>A series of pyrazole amides was synthesized and screened for JNK-1 inhibitory and anti-inflammatory activity. Docking study was also performed.
Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10μM, in particular compounds 9c, 10a and 10d were found to be potent among all the compounds.</description><subject>Amides - chemistry</subject><subject>Amides - pharmacology</subject><subject>Amides - therapeutic use</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Edema - drug therapy</subject><subject>Humans</subject><subject>IC50</subject><subject>Inflammation</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - chemistry</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>JNK-1</subject><subject>Molecular Docking Simulation</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Pyrazoles</subject><subject>Pyrazoles - chemistry</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrazoles - therapeutic use</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1vFDEURS0EIpuEH0CDXNLM4GePvTZUURQCKCKIhNry2G8UL_Ox2J6VNr-eWW2ghOa-5txbvEPIa2A1MFDvNnU7-JozaGqma8b1M7KCRjWVEAaekxUzSldMG3VCTnPeMMZ4Y-AlOeGSKzDcrIj9tk_uceqRBkxx50rcYaYu0-1UcCw0jg-xjWVKmU4d9dWXeaRfq4JpiKPr6c8lM76nd_uxPGCOS3UM9O7iO81lDhHzOXnRuT7jq6d7Rn58vLq__FTd3F5_vry4qbzQqlRK8qC5kQA6GC6DZKwVbu1BuqbTvAseO-5hbQywBrADxsPaY9MJ4VumuDgjb4-72zT9mjEXO8Tsse_diNOcLSghmZCH-D_KjVFcS72gcER9mnJO2NltioNLewvMHhTYjV0U2IMCy7RdFCydN0_zcztg-Nv48_MF-HAEcPnHLmKy2UccPYaY0BcbpviP-d9tC5Xz</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Doma, Anuradha</creator><creator>Kulkarni, Ravindra</creator><creator>Palakodety, Radhakrishna</creator><creator>Sastry, G. Narahari</creator><creator>Sridhara, Janardhan</creator><creator>Garlapati, Achaiah</creator><general>Elsevier Ltd</general><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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20141101</creationdate><title>Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies</title><author>Doma, Anuradha ; Kulkarni, Ravindra ; Palakodety, Radhakrishna ; Sastry, G. Narahari ; Sridhara, Janardhan ; Garlapati, Achaiah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-652d8295118d925d500b3a7c15a4f82fdcef2c17991041ef102d7ce4f33cb0623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amides - chemistry</topic><topic>Amides - pharmacology</topic><topic>Amides - therapeutic use</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Edema - drug therapy</topic><topic>Humans</topic><topic>IC50</topic><topic>Inflammation</topic><topic>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>JNK Mitogen-Activated Protein Kinases - chemistry</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>JNK-1</topic><topic>Molecular Docking Simulation</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Pyrazoles</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrazoles - therapeutic use</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Doma, Anuradha</creatorcontrib><creatorcontrib>Kulkarni, Ravindra</creatorcontrib><creatorcontrib>Palakodety, Radhakrishna</creatorcontrib><creatorcontrib>Sastry, G. Narahari</creatorcontrib><creatorcontrib>Sridhara, Janardhan</creatorcontrib><creatorcontrib>Garlapati, Achaiah</creatorcontrib><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Doma, Anuradha</au><au>Kulkarni, Ravindra</au><au>Palakodety, Radhakrishna</au><au>Sastry, G. Narahari</au><au>Sridhara, Janardhan</au><au>Garlapati, Achaiah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>22</volume><issue>21</issue><spage>6209</spage><epage>6219</epage><pages>6209-6219</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>A series of pyrazole amides was synthesized and screened for JNK-1 inhibitory and anti-inflammatory activity. Docking study was also performed.
Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10μM, in particular compounds 9c, 10a and 10d were found to be potent among all the compounds.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25261929</pmid><doi>10.1016/j.bmc.2014.08.028</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2014-11, Vol.22 (21), p.6209-6219 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1635035350 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amides - chemistry Amides - pharmacology Amides - therapeutic use Animals Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Edema - drug therapy Humans IC50 Inflammation JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - chemistry JNK Mitogen-Activated Protein Kinases - metabolism JNK-1 Molecular Docking Simulation Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Pyrazoles Pyrazoles - chemistry Pyrazoles - pharmacology Pyrazoles - therapeutic use Rats Structure-Activity Relationship |
| title | Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T12%3A56%3A23IST&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=Pyrazole%20derivatives%20as%20potent%20inhibitors%20of%20c-Jun%20N-terminal%20kinase:%20Synthesis%20and%20SAR%20studies&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Doma,%20Anuradha&rft.date=2014-11-01&rft.volume=22&rft.issue=21&rft.spage=6209&rft.epage=6219&rft.pages=6209-6219&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2014.08.028&rft_dat=%3Cproquest_cross%3E1635035350%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=1629962858&rft_id=info:pmid/25261929&rft_els_id=S0968089614006154&rfr_iscdi=true |