Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular-Modeling Studies
Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX‐2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3‐pyrazolyl‐substituted benzotriazinones as anti‐inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a–c a...
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| Veröffentlicht in: | Archiv der Pharmazie (Weinheim) 2010-11, Vol.343 (11-12), p.631-638 |
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| creator | Raffa, Demetrio Migliara, Onofrio Maggio, Benedetta Plescia, Fabiana Cascioferro, Stella Cusimano, Maria Grazia Tringali, Giuseppe Cannizzaro, Carla Plescia, Fulvio |
| description | Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX‐2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3‐pyrazolyl‐substituted benzotriazinones as anti‐inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a–c and 18a–c have been prepared by reacting the opportune ethyl 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxylate or 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5‐(4‐oxo‐1,2,3‐benzotriazin‐3(4H)‐yl)‐1‐pyridin‐2‐yl‐1H‐pyrazole‐4‐carboxylate, a good COX‐1/COX‐2 selectivity. Molecular modeling studies confirmed the obtained biological results.
Gastrolesivity in all those therapies associated to an inflammatory process calls for the availability of new anti‐inflammatory agents. Therefore, new pyrazolylbenzotriazinones were synthesized and tested for their COX‐1 and COX‐2 inhibitory activities. |
| doi_str_mv | 10.1002/ardp.200900317 |
| format | Article |
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Gastrolesivity in all those therapies associated to an inflammatory process calls for the availability of new anti‐inflammatory agents. Therefore, new pyrazolylbenzotriazinones were synthesized and tested for their COX‐1 and COX‐2 inhibitory activities.</description><identifier>ISSN: 0365-6233</identifier><identifier>EISSN: 1521-4184</identifier><identifier>DOI: 10.1002/ardp.200900317</identifier><identifier>PMID: 21110338</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>2-(1H-Pyrazol-1-yl)pyridines ; 4(3H)-Benzotriazinones ; Anti-Inflammatory Agents - chemical synthesis ; Anti-Inflammatory Agents - pharmacology ; Celecoxib ; COX-2 inhibitors ; Cyclooxygenase 2 Inhibitors - chemical synthesis ; Cyclooxygenase 2 Inhibitors - chemistry ; Docking ; Humans ; Models, Molecular ; Pyrazoles ; Structure-Activity Relationship ; Sulfonamides ; Triazines - pharmacology</subject><ispartof>Archiv der Pharmazie (Weinheim), 2010-11, Vol.343 (11-12), p.631-638</ispartof><rights>Copyright © 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4887-36905bf3b617f0181c3fa0e4c4e3983efad2d6b98e2d43d9bb186a3895e50ea03</citedby><cites>FETCH-LOGICAL-c4887-36905bf3b617f0181c3fa0e4c4e3983efad2d6b98e2d43d9bb186a3895e50ea03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fardp.200900317$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fardp.200900317$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21110338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raffa, Demetrio</creatorcontrib><creatorcontrib>Migliara, Onofrio</creatorcontrib><creatorcontrib>Maggio, Benedetta</creatorcontrib><creatorcontrib>Plescia, Fabiana</creatorcontrib><creatorcontrib>Cascioferro, Stella</creatorcontrib><creatorcontrib>Cusimano, Maria Grazia</creatorcontrib><creatorcontrib>Tringali, Giuseppe</creatorcontrib><creatorcontrib>Cannizzaro, Carla</creatorcontrib><creatorcontrib>Plescia, Fulvio</creatorcontrib><title>Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular-Modeling Studies</title><title>Archiv der Pharmazie (Weinheim)</title><addtitle>Arch. Pharm. Pharm. Med. Chem</addtitle><description>Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX‐2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3‐pyrazolyl‐substituted benzotriazinones as anti‐inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a–c and 18a–c have been prepared by reacting the opportune ethyl 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxylate or 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5‐(4‐oxo‐1,2,3‐benzotriazin‐3(4H)‐yl)‐1‐pyridin‐2‐yl‐1H‐pyrazole‐4‐carboxylate, a good COX‐1/COX‐2 selectivity. Molecular modeling studies confirmed the obtained biological results.
Gastrolesivity in all those therapies associated to an inflammatory process calls for the availability of new anti‐inflammatory agents. Therefore, new pyrazolylbenzotriazinones were synthesized and tested for their COX‐1 and COX‐2 inhibitory activities.</description><subject>2-(1H-Pyrazol-1-yl)pyridines</subject><subject>4(3H)-Benzotriazinones</subject><subject>Anti-Inflammatory Agents - chemical synthesis</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Celecoxib</subject><subject>COX-2 inhibitors</subject><subject>Cyclooxygenase 2 Inhibitors - chemical synthesis</subject><subject>Cyclooxygenase 2 Inhibitors - chemistry</subject><subject>Docking</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Pyrazoles</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides</subject><subject>Triazines - pharmacology</subject><issn>0365-6233</issn><issn>1521-4184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM9v0zAYhi0E2srYlSPyjctS_DNxuLUdHZM2Nm1DQ1wsJ_6yGdy4s5NB-teTqaPixum9PM9zeBF6S8mUEsI-mGjXU0ZISQinxQs0oZLRTFAlXqIJ4bnMcsb5Pnqd0g8yMoTJPbTPKKWEczVB_eUQzSb4UEG7CV10ZuPa0AI-hugeTeceIWGT8OLiGz5t713luhDTR3w9tN09JJeO8NyN-p2rjcezehRcNxxh01p8HjzUvTcxOw8WvGvv8HXXWwfpDXrVGJ_g8HkP0Nflp5vF5-zs4uR0MTvLaqFUkfG8JLJqeJXToiFU0Zo3hoCoBfBScWiMZTavSgXMCm7LqqIqN1yVEiQBQ_gBer_trmN46CF1euVSDd6bFkKftKJSilwoNpLTLVnHkFKERq-jW5k4aEr009P66Wm9e3oU3j2n-2oFdof_vXYEyi3wy3kY_pPTs6vjy3_j2dZ1qYPfO9fEnzoveCH17ZcTXdyW8-VSzPV3_geMz5uc</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Raffa, Demetrio</creator><creator>Migliara, Onofrio</creator><creator>Maggio, Benedetta</creator><creator>Plescia, Fabiana</creator><creator>Cascioferro, Stella</creator><creator>Cusimano, Maria Grazia</creator><creator>Tringali, Giuseppe</creator><creator>Cannizzaro, Carla</creator><creator>Plescia, Fulvio</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>BSCLL</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>201011</creationdate><title>Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular-Modeling Studies</title><author>Raffa, Demetrio ; Migliara, Onofrio ; Maggio, Benedetta ; Plescia, Fabiana ; Cascioferro, Stella ; Cusimano, Maria Grazia ; Tringali, Giuseppe ; Cannizzaro, Carla ; Plescia, Fulvio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4887-36905bf3b617f0181c3fa0e4c4e3983efad2d6b98e2d43d9bb186a3895e50ea03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>2-(1H-Pyrazol-1-yl)pyridines</topic><topic>4(3H)-Benzotriazinones</topic><topic>Anti-Inflammatory Agents - chemical synthesis</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Celecoxib</topic><topic>COX-2 inhibitors</topic><topic>Cyclooxygenase 2 Inhibitors - chemical synthesis</topic><topic>Cyclooxygenase 2 Inhibitors - chemistry</topic><topic>Docking</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Pyrazoles</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides</topic><topic>Triazines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raffa, Demetrio</creatorcontrib><creatorcontrib>Migliara, Onofrio</creatorcontrib><creatorcontrib>Maggio, Benedetta</creatorcontrib><creatorcontrib>Plescia, Fabiana</creatorcontrib><creatorcontrib>Cascioferro, Stella</creatorcontrib><creatorcontrib>Cusimano, Maria Grazia</creatorcontrib><creatorcontrib>Tringali, Giuseppe</creatorcontrib><creatorcontrib>Cannizzaro, Carla</creatorcontrib><creatorcontrib>Plescia, Fulvio</creatorcontrib><collection>Istex</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>Archiv der Pharmazie (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raffa, Demetrio</au><au>Migliara, Onofrio</au><au>Maggio, Benedetta</au><au>Plescia, Fabiana</au><au>Cascioferro, Stella</au><au>Cusimano, Maria Grazia</au><au>Tringali, Giuseppe</au><au>Cannizzaro, Carla</au><au>Plescia, Fulvio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular-Modeling Studies</atitle><jtitle>Archiv der Pharmazie (Weinheim)</jtitle><addtitle>Arch. Pharm. Pharm. Med. Chem</addtitle><date>2010-11</date><risdate>2010</risdate><volume>343</volume><issue>11-12</issue><spage>631</spage><epage>638</epage><pages>631-638</pages><issn>0365-6233</issn><eissn>1521-4184</eissn><abstract>Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX‐2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3‐pyrazolyl‐substituted benzotriazinones as anti‐inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a–c and 18a–c have been prepared by reacting the opportune ethyl 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxylate or 5‐(2‐aminobenzamido)‐1‐(pyridin‐2‐yl)‐1H‐pyrazole‐4‐carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5‐(4‐oxo‐1,2,3‐benzotriazin‐3(4H)‐yl)‐1‐pyridin‐2‐yl‐1H‐pyrazole‐4‐carboxylate, a good COX‐1/COX‐2 selectivity. Molecular modeling studies confirmed the obtained biological results.
Gastrolesivity in all those therapies associated to an inflammatory process calls for the availability of new anti‐inflammatory agents. Therefore, new pyrazolylbenzotriazinones were synthesized and tested for their COX‐1 and COX‐2 inhibitory activities.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>21110338</pmid><doi>10.1002/ardp.200900317</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2-(1H-Pyrazol-1-yl)pyridines 4(3H)-Benzotriazinones Anti-Inflammatory Agents - chemical synthesis Anti-Inflammatory Agents - pharmacology Celecoxib COX-2 inhibitors Cyclooxygenase 2 Inhibitors - chemical synthesis Cyclooxygenase 2 Inhibitors - chemistry Docking Humans Models, Molecular Pyrazoles Structure-Activity Relationship Sulfonamides Triazines - pharmacology |
| title | Pyrazolobenzotriazinone Derivatives as COX Inhibitors: Synthesis, Biological Activity, and Molecular-Modeling Studies |
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