Synthesis and biological evaluation of indazole derivatives
The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference, E rel, bet...
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| Veröffentlicht in: | European journal of medicinal chemistry 2011-04, Vol.46 (4), p.1439-1447 |
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| container_title | European journal of medicinal chemistry |
| container_volume | 46 |
| creator | Claramunt, Rosa M. López, Concepción López, Ana Pérez-Medina, Carlos Pérez-Torralba, Marta Alkorta, Ibon Elguero, José Escames, Germaine Acuña-Castroviejo, Darío |
| description | The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference,
E
rel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.
[Display omitted]
► synthetic indazoles are good inhibitors of NOS isoforms. ► fluorine atoms in the molecule increase the inhibitory potency against NOS. ► 4,5,6,7-tetrafluoroindazole is a potent and selective iNOS inhibitor. ► a parabolic model relates the interaction between inhibitory indazoles and iNOS. |
| doi_str_mv | 10.1016/j.ejmech.2011.01.027 |
| format | Article |
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E
rel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.
[Display omitted]
► synthetic indazoles are good inhibitors of NOS isoforms. ► fluorine atoms in the molecule increase the inhibitory potency against NOS. ► 4,5,6,7-tetrafluoroindazole is a potent and selective iNOS inhibitor. ► a parabolic model relates the interaction between inhibitory indazoles and iNOS.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2011.01.027</identifier><identifier>PMID: 21334118</identifier><identifier>CODEN: EJMCA5</identifier><language>eng</language><publisher>Kidlington: Elsevier Masson SAS</publisher><subject>Biological and medical sciences ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Indazoles ; Indazoles - chemical synthesis ; Indazoles - chemistry ; Indazoles - pharmacology ; iNOS ; Medical sciences ; Miscellaneous ; Modeling ; Nitric Oxide Synthase Type I - antagonists & inhibitors ; Nitric Oxide Synthase Type II - antagonists & inhibitors ; nNOS ; Pharmacology. Drug treatments</subject><ispartof>European journal of medicinal chemistry, 2011-04, Vol.46 (4), p.1439-1447</ispartof><rights>2011 Elsevier Masson SAS</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-cc0d6e3b87dda466df18776810dc8c0e4cddfdea4be10eb5585a467782aabae53</citedby><cites>FETCH-LOGICAL-c391t-cc0d6e3b87dda466df18776810dc8c0e4cddfdea4be10eb5585a467782aabae53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2011.01.027$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23969359$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21334118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Claramunt, Rosa M.</creatorcontrib><creatorcontrib>López, Concepción</creatorcontrib><creatorcontrib>López, Ana</creatorcontrib><creatorcontrib>Pérez-Medina, Carlos</creatorcontrib><creatorcontrib>Pérez-Torralba, Marta</creatorcontrib><creatorcontrib>Alkorta, Ibon</creatorcontrib><creatorcontrib>Elguero, José</creatorcontrib><creatorcontrib>Escames, Germaine</creatorcontrib><creatorcontrib>Acuña-Castroviejo, Darío</creatorcontrib><title>Synthesis and biological evaluation of indazole derivatives</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference,
E
rel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.
[Display omitted]
► synthetic indazoles are good inhibitors of NOS isoforms. ► fluorine atoms in the molecule increase the inhibitory potency against NOS. ► 4,5,6,7-tetrafluoroindazole is a potent and selective iNOS inhibitor. ► a parabolic model relates the interaction between inhibitory indazoles and iNOS.</description><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Indazoles</subject><subject>Indazoles - chemical synthesis</subject><subject>Indazoles - chemistry</subject><subject>Indazoles - pharmacology</subject><subject>iNOS</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Modeling</subject><subject>Nitric Oxide Synthase Type I - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase Type II - antagonists & inhibitors</subject><subject>nNOS</subject><subject>Pharmacology. Drug treatments</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMobk7_gUhvxKvWfDRtiiDI8AsGXqjXIU1OXUbXzKQdzF9vxqbeCQcOHJ5zzsuD0DnBGcGkuF5ksFiCnmcUE5LhWLQ8QGNSFiJllOeHaIwpZSmnLB-hkxAWGGNeYHyMRpQwlhMixujmddP1cwg2JKozSW1d6z6sVm0Ca9UOqreuS1yT2M6oL9dCYsDbdRyvIZyio0a1Ac72fYLeH-7fpk_p7OXxeXo3SzWrSJ9qjU0BrBalMSovCtMQUcaUBBstNIZcG9MYUHkNBEPNueARK0tBlaoVcDZBV7u7K-8-Bwi9XNqgoW1VB24IUnAeHZSERjLfkdq7EDw0cuXtUvmNJFhurcmF3FmTW2sSx6JlXLvYPxjqJZjfpR9NEbjcAypEN41Xnbbhj2NVUTFeRe52x0HUsbbgZdAWOg3GetC9NM7-n-Qb1XCNaQ</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Claramunt, Rosa M.</creator><creator>López, Concepción</creator><creator>López, Ana</creator><creator>Pérez-Medina, Carlos</creator><creator>Pérez-Torralba, Marta</creator><creator>Alkorta, Ibon</creator><creator>Elguero, José</creator><creator>Escames, Germaine</creator><creator>Acuña-Castroviejo, Darío</creator><general>Elsevier Masson SAS</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>20110401</creationdate><title>Synthesis and biological evaluation of indazole derivatives</title><author>Claramunt, Rosa M. ; López, Concepción ; López, Ana ; Pérez-Medina, Carlos ; Pérez-Torralba, Marta ; Alkorta, Ibon ; Elguero, José ; Escames, Germaine ; Acuña-Castroviejo, Darío</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-cc0d6e3b87dda466df18776810dc8c0e4cddfdea4be10eb5585a467782aabae53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Indazoles</topic><topic>Indazoles - chemical synthesis</topic><topic>Indazoles - chemistry</topic><topic>Indazoles - pharmacology</topic><topic>iNOS</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Modeling</topic><topic>Nitric Oxide Synthase Type I - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase Type II - antagonists & inhibitors</topic><topic>nNOS</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Claramunt, Rosa M.</creatorcontrib><creatorcontrib>López, Concepción</creatorcontrib><creatorcontrib>López, Ana</creatorcontrib><creatorcontrib>Pérez-Medina, Carlos</creatorcontrib><creatorcontrib>Pérez-Torralba, Marta</creatorcontrib><creatorcontrib>Alkorta, Ibon</creatorcontrib><creatorcontrib>Elguero, José</creatorcontrib><creatorcontrib>Escames, Germaine</creatorcontrib><creatorcontrib>Acuña-Castroviejo, Darío</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>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Claramunt, Rosa M.</au><au>López, Concepción</au><au>López, Ana</au><au>Pérez-Medina, Carlos</au><au>Pérez-Torralba, Marta</au><au>Alkorta, Ibon</au><au>Elguero, José</au><au>Escames, Germaine</au><au>Acuña-Castroviejo, Darío</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation of indazole derivatives</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>46</volume><issue>4</issue><spage>1439</spage><epage>1447</epage><pages>1439-1447</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><coden>EJMCA5</coden><abstract>The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference,
E
rel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.
[Display omitted]
► synthetic indazoles are good inhibitors of NOS isoforms. ► fluorine atoms in the molecule increase the inhibitory potency against NOS. ► 4,5,6,7-tetrafluoroindazole is a potent and selective iNOS inhibitor. ► a parabolic model relates the interaction between inhibitory indazoles and iNOS.</abstract><cop>Kidlington</cop><pub>Elsevier Masson SAS</pub><pmid>21334118</pmid><doi>10.1016/j.ejmech.2011.01.027</doi><tpages>9</tpages></addata></record> |
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| subjects | Biological and medical sciences Dose-Response Relationship, Drug Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Indazoles Indazoles - chemical synthesis Indazoles - chemistry Indazoles - pharmacology iNOS Medical sciences Miscellaneous Modeling Nitric Oxide Synthase Type I - antagonists & inhibitors Nitric Oxide Synthase Type II - antagonists & inhibitors nNOS Pharmacology. Drug treatments |
| title | Synthesis and biological evaluation of indazole derivatives |
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