Nonsteroidal Selective Glucocorticoid Modulators: The Effect of C-10 Substitution on Receptor Selectivity and Functional Potency of 5-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines
The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-a...
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| Veröffentlicht in: | Journal of medicinal chemistry 2003-03, Vol.46 (6), p.1016-1030 |
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| creator | Kym, Philip R Kort, Michael E Coghlan, Michael J Moore, Jimmie L Tang, Rui Ratajczyk, James D Larson, Daniel P Elmore, Steven W Pratt, John K Stashko, Michael A Falls, H. Douglass Lin, Chun W Nakane, Masake Miller, Loan Tyree, Curtis M Miner, Jeffery N Jacobson, Peer B Wilcox, Denise M Nguyen, Phong Lane, Benjamin C |
| description | The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-atom appendages (OCH3, OCF2H, NHMe, SMe, CHCH2, C⋮CH, CH2OH) provided molecules of high affinity (K i = 2−8 nM) for the human glucocorticoid receptor (hGR) with limited cross-reactivity with other steroid receptors (PR, MR, AR, ER). Optimal analogues showed slightly less potent but highly efficacious E-selectin repression with reduced levels of GRE activation efficacy in reporter gene assays relative to prednisolone. Preliminary SAR of analogues containing substitution at the C-9 and C-10 positions identified the 9-OH, 10-OMe analogue 50 and the 9-OH, 10-Cl analogue 58 as compounds that demonstrated potent, GR-mediated inhibition in a conconavalin A stimulated T-cell proliferation assay in both rodent and human whole blood monocytes. When evaluated for their in vivo effects in carrageenan-induced paw edema in rats, 50, 58, and 10-OCF2H analogue 35 showed dose-dependent anti-inflammatory effects (50, ED50 = 16 mg/kg; 58, ED50 = 15 mg/kg; 35, ED50 = 21 mg/kg vs ED50 = 15 mg/kg for 18 and ED50 = 4 mg/kg for prednisolone). |
| doi_str_mv | 10.1021/jm020335m |
| format | Article |
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Douglass ; Lin, Chun W ; Nakane, Masake ; Miller, Loan ; Tyree, Curtis M ; Miner, Jeffery N ; Jacobson, Peer B ; Wilcox, Denise M ; Nguyen, Phong ; Lane, Benjamin C</creator><creatorcontrib>Kym, Philip R ; Kort, Michael E ; Coghlan, Michael J ; Moore, Jimmie L ; Tang, Rui ; Ratajczyk, James D ; Larson, Daniel P ; Elmore, Steven W ; Pratt, John K ; Stashko, Michael A ; Falls, H. Douglass ; Lin, Chun W ; Nakane, Masake ; Miller, Loan ; Tyree, Curtis M ; Miner, Jeffery N ; Jacobson, Peer B ; Wilcox, Denise M ; Nguyen, Phong ; Lane, Benjamin C</creatorcontrib><description>The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-atom appendages (OCH3, OCF2H, NHMe, SMe, CHCH2, C⋮CH, CH2OH) provided molecules of high affinity (K i = 2−8 nM) for the human glucocorticoid receptor (hGR) with limited cross-reactivity with other steroid receptors (PR, MR, AR, ER). Optimal analogues showed slightly less potent but highly efficacious E-selectin repression with reduced levels of GRE activation efficacy in reporter gene assays relative to prednisolone. Preliminary SAR of analogues containing substitution at the C-9 and C-10 positions identified the 9-OH, 10-OMe analogue 50 and the 9-OH, 10-Cl analogue 58 as compounds that demonstrated potent, GR-mediated inhibition in a conconavalin A stimulated T-cell proliferation assay in both rodent and human whole blood monocytes. When evaluated for their in vivo effects in carrageenan-induced paw edema in rats, 50, 58, and 10-OCF2H analogue 35 showed dose-dependent anti-inflammatory effects (50, ED50 = 16 mg/kg; 58, ED50 = 15 mg/kg; 35, ED50 = 21 mg/kg vs ED50 = 15 mg/kg for 18 and ED50 = 4 mg/kg for prednisolone).</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm020335m</identifier><identifier>PMID: 12620078</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Allyl Compounds - chemical synthesis ; Allyl Compounds - chemistry ; Allyl Compounds - pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Binding, Competitive ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Carrageenan ; Cell Division - drug effects ; Concanavalin A - pharmacology ; E-Selectin - genetics ; E-Selectin - metabolism ; Edema - chemically induced ; Edema - drug therapy ; Humans ; In Vitro Techniques ; Ligands ; Medical sciences ; NF-kappa B - metabolism ; Pharmacology. Drug treatments ; Protein Isoforms ; Quinolines - chemical synthesis ; Quinolines - chemistry ; Quinolines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid - drug effects ; Receptors, Glucocorticoid - genetics ; Receptors, Glucocorticoid - metabolism ; Response Elements ; Species Specificity ; Structure-Activity Relationship ; T-Lymphocytes - cytology ; T-Lymphocytes - drug effects ; Transcription Factor AP-1 - metabolism ; Transcription, Genetic</subject><ispartof>Journal of medicinal chemistry, 2003-03, Vol.46 (6), p.1016-1030</ispartof><rights>Copyright © 2003 American Chemical Society</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a377t-f473ccd3289e275af7825e5b779fd9577fa36b85114a7ed0d98ee47d4cccb8053</citedby><cites>FETCH-LOGICAL-a377t-f473ccd3289e275af7825e5b779fd9577fa36b85114a7ed0d98ee47d4cccb8053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm020335m$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm020335m$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,777,781,2752,27057,27905,27906,56719,56769</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14640155$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12620078$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kym, Philip R</creatorcontrib><creatorcontrib>Kort, Michael E</creatorcontrib><creatorcontrib>Coghlan, Michael J</creatorcontrib><creatorcontrib>Moore, Jimmie L</creatorcontrib><creatorcontrib>Tang, Rui</creatorcontrib><creatorcontrib>Ratajczyk, James D</creatorcontrib><creatorcontrib>Larson, Daniel P</creatorcontrib><creatorcontrib>Elmore, Steven W</creatorcontrib><creatorcontrib>Pratt, John K</creatorcontrib><creatorcontrib>Stashko, Michael A</creatorcontrib><creatorcontrib>Falls, H. Douglass</creatorcontrib><creatorcontrib>Lin, Chun W</creatorcontrib><creatorcontrib>Nakane, Masake</creatorcontrib><creatorcontrib>Miller, Loan</creatorcontrib><creatorcontrib>Tyree, Curtis M</creatorcontrib><creatorcontrib>Miner, Jeffery N</creatorcontrib><creatorcontrib>Jacobson, Peer B</creatorcontrib><creatorcontrib>Wilcox, Denise M</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Lane, Benjamin C</creatorcontrib><title>Nonsteroidal Selective Glucocorticoid Modulators: The Effect of C-10 Substitution on Receptor Selectivity and Functional Potency of 5-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-atom appendages (OCH3, OCF2H, NHMe, SMe, CHCH2, C⋮CH, CH2OH) provided molecules of high affinity (K i = 2−8 nM) for the human glucocorticoid receptor (hGR) with limited cross-reactivity with other steroid receptors (PR, MR, AR, ER). Optimal analogues showed slightly less potent but highly efficacious E-selectin repression with reduced levels of GRE activation efficacy in reporter gene assays relative to prednisolone. Preliminary SAR of analogues containing substitution at the C-9 and C-10 positions identified the 9-OH, 10-OMe analogue 50 and the 9-OH, 10-Cl analogue 58 as compounds that demonstrated potent, GR-mediated inhibition in a conconavalin A stimulated T-cell proliferation assay in both rodent and human whole blood monocytes. When evaluated for their in vivo effects in carrageenan-induced paw edema in rats, 50, 58, and 10-OCF2H analogue 35 showed dose-dependent anti-inflammatory effects (50, ED50 = 16 mg/kg; 58, ED50 = 15 mg/kg; 35, ED50 = 21 mg/kg vs ED50 = 15 mg/kg for 18 and ED50 = 4 mg/kg for prednisolone).</description><subject>Allyl Compounds - chemical synthesis</subject><subject>Allyl Compounds - chemistry</subject><subject>Allyl Compounds - pharmacology</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Carrageenan</subject><subject>Cell Division - drug effects</subject><subject>Concanavalin A - pharmacology</subject><subject>E-Selectin - genetics</subject><subject>E-Selectin - metabolism</subject><subject>Edema - chemically induced</subject><subject>Edema - drug therapy</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>NF-kappa B - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Isoforms</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glucocorticoid - drug effects</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Response Elements</subject><subject>Species Specificity</subject><subject>Structure-Activity Relationship</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - drug effects</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Transcription, Genetic</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkctuEzEUhkcIRENhwQug2YCEVIMv4_GEXRV6QUqhIgEWVWV5fFGcOuPU9iCGFVsejpfgSXCUKNkgWTqW_8-_z_FfFM8RfIMgRm-XK4ghIXT1oBghiiGoGlg9LEYQYgxwjclR8STGJYSQIEweF0coH0LImlHx56PvYtLBWyVcOdNOy2S_6_LC9dJLH5KVWSqvvOqdSD7Ed39__S7nC12eGZPZ0ptyAhAsZ30bk019sr4r8_qspV7nC3tPm4ZSdKo87zu5gfJz1z7pTg4bDwpOnRscwCcUKLsYVPB5j08qkIJd6bTIGroEN-i21d1Pvx6C6PwNybq5ve9t553tdHxaPDLCRf1sV4-LL-dn88klmH66-DA5nQJBGEvAVIxIqQhuxhozKgxrMNW0ZWxs1JgyZgSp24YiVAmmFVTjRuuKqUpK2TaQkuPi1dZ3Hfx9r2PiKxuldk502veRMwJZXeEmg6-3oAw-xqANX-dxRBg4gnyTHd9nl9kXO9O-XWl1IHdhZeDlDhBRCmfyF0gbD1xVVxDRTXdgy9mc7I-9LsIdrxlhlM-vZ_wbwVfv8dcprw--Qka-9H3I2cT_NPgPvN6_bg</recordid><startdate>20030313</startdate><enddate>20030313</enddate><creator>Kym, Philip R</creator><creator>Kort, Michael E</creator><creator>Coghlan, Michael J</creator><creator>Moore, Jimmie L</creator><creator>Tang, Rui</creator><creator>Ratajczyk, James D</creator><creator>Larson, Daniel P</creator><creator>Elmore, Steven W</creator><creator>Pratt, John K</creator><creator>Stashko, Michael A</creator><creator>Falls, H. Douglass</creator><creator>Lin, Chun W</creator><creator>Nakane, Masake</creator><creator>Miller, Loan</creator><creator>Tyree, Curtis M</creator><creator>Miner, Jeffery N</creator><creator>Jacobson, Peer B</creator><creator>Wilcox, Denise M</creator><creator>Nguyen, Phong</creator><creator>Lane, Benjamin C</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>20030313</creationdate><title>Nonsteroidal Selective Glucocorticoid Modulators: The Effect of C-10 Substitution on Receptor Selectivity and Functional Potency of 5-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines</title><author>Kym, Philip R ; Kort, Michael E ; Coghlan, Michael J ; Moore, Jimmie L ; Tang, Rui ; Ratajczyk, James D ; Larson, Daniel P ; Elmore, Steven W ; Pratt, John K ; Stashko, Michael A ; Falls, H. Douglass ; Lin, Chun W ; Nakane, Masake ; Miller, Loan ; Tyree, Curtis M ; Miner, Jeffery N ; Jacobson, Peer B ; Wilcox, Denise M ; Nguyen, Phong ; Lane, Benjamin C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a377t-f473ccd3289e275af7825e5b779fd9577fa36b85114a7ed0d98ee47d4cccb8053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Allyl Compounds - chemical synthesis</topic><topic>Allyl Compounds - chemistry</topic><topic>Allyl Compounds - pharmacology</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Carrageenan</topic><topic>Cell Division - drug effects</topic><topic>Concanavalin A - pharmacology</topic><topic>E-Selectin - genetics</topic><topic>E-Selectin - metabolism</topic><topic>Edema - chemically induced</topic><topic>Edema - drug therapy</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>NF-kappa B - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Isoforms</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - chemistry</topic><topic>Quinolines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Glucocorticoid - drug effects</topic><topic>Receptors, Glucocorticoid - genetics</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Response Elements</topic><topic>Species Specificity</topic><topic>Structure-Activity Relationship</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - drug effects</topic><topic>Transcription Factor AP-1 - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kym, Philip R</creatorcontrib><creatorcontrib>Kort, Michael E</creatorcontrib><creatorcontrib>Coghlan, Michael J</creatorcontrib><creatorcontrib>Moore, Jimmie L</creatorcontrib><creatorcontrib>Tang, Rui</creatorcontrib><creatorcontrib>Ratajczyk, James D</creatorcontrib><creatorcontrib>Larson, Daniel P</creatorcontrib><creatorcontrib>Elmore, Steven W</creatorcontrib><creatorcontrib>Pratt, John K</creatorcontrib><creatorcontrib>Stashko, Michael A</creatorcontrib><creatorcontrib>Falls, H. Douglass</creatorcontrib><creatorcontrib>Lin, Chun W</creatorcontrib><creatorcontrib>Nakane, Masake</creatorcontrib><creatorcontrib>Miller, Loan</creatorcontrib><creatorcontrib>Tyree, Curtis M</creatorcontrib><creatorcontrib>Miner, Jeffery N</creatorcontrib><creatorcontrib>Jacobson, Peer B</creatorcontrib><creatorcontrib>Wilcox, Denise M</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Lane, Benjamin C</creatorcontrib><collection>Istex</collection><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>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kym, Philip R</au><au>Kort, Michael E</au><au>Coghlan, Michael J</au><au>Moore, Jimmie L</au><au>Tang, Rui</au><au>Ratajczyk, James D</au><au>Larson, Daniel P</au><au>Elmore, Steven W</au><au>Pratt, John K</au><au>Stashko, Michael A</au><au>Falls, H. Douglass</au><au>Lin, Chun W</au><au>Nakane, Masake</au><au>Miller, Loan</au><au>Tyree, Curtis M</au><au>Miner, Jeffery N</au><au>Jacobson, Peer B</au><au>Wilcox, Denise M</au><au>Nguyen, Phong</au><au>Lane, Benjamin C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonsteroidal Selective Glucocorticoid Modulators: The Effect of C-10 Substitution on Receptor Selectivity and Functional Potency of 5-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2003-03-13</date><risdate>2003</risdate><volume>46</volume><issue>6</issue><spage>1016</spage><epage>1030</epage><pages>1016-1030</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-atom appendages (OCH3, OCF2H, NHMe, SMe, CHCH2, C⋮CH, CH2OH) provided molecules of high affinity (K i = 2−8 nM) for the human glucocorticoid receptor (hGR) with limited cross-reactivity with other steroid receptors (PR, MR, AR, ER). Optimal analogues showed slightly less potent but highly efficacious E-selectin repression with reduced levels of GRE activation efficacy in reporter gene assays relative to prednisolone. Preliminary SAR of analogues containing substitution at the C-9 and C-10 positions identified the 9-OH, 10-OMe analogue 50 and the 9-OH, 10-Cl analogue 58 as compounds that demonstrated potent, GR-mediated inhibition in a conconavalin A stimulated T-cell proliferation assay in both rodent and human whole blood monocytes. When evaluated for their in vivo effects in carrageenan-induced paw edema in rats, 50, 58, and 10-OCF2H analogue 35 showed dose-dependent anti-inflammatory effects (50, ED50 = 16 mg/kg; 58, ED50 = 15 mg/kg; 35, ED50 = 21 mg/kg vs ED50 = 15 mg/kg for 18 and ED50 = 4 mg/kg for prednisolone).</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>12620078</pmid><doi>10.1021/jm020335m</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2003-03, Vol.46 (6), p.1016-1030 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73076428 |
| source | MEDLINE; ACS Publications |
| subjects | Allyl Compounds - chemical synthesis Allyl Compounds - chemistry Allyl Compounds - pharmacology Animals Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology Binding, Competitive Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Carrageenan Cell Division - drug effects Concanavalin A - pharmacology E-Selectin - genetics E-Selectin - metabolism Edema - chemically induced Edema - drug therapy Humans In Vitro Techniques Ligands Medical sciences NF-kappa B - metabolism Pharmacology. Drug treatments Protein Isoforms Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacology Rats Rats, Sprague-Dawley Receptors, Glucocorticoid - drug effects Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism Response Elements Species Specificity Structure-Activity Relationship T-Lymphocytes - cytology T-Lymphocytes - drug effects Transcription Factor AP-1 - metabolism Transcription, Genetic |
| title | Nonsteroidal Selective Glucocorticoid Modulators: The Effect of C-10 Substitution on Receptor Selectivity and Functional Potency of 5-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T09%3A35%3A54IST&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=Nonsteroidal%20Selective%20Glucocorticoid%20Modulators:%E2%80%89%20The%20Effect%20of%20C-10%20Substitution%20on%20Receptor%20Selectivity%20and%20Functional%20Potency%20of%205-Allyl-2,5-dihydro-2,2,4-trimethyl-1H-%5B1%5Dbenzopyrano%5B3,4-f%5Dquinolines&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Kym,%20Philip%20R&rft.date=2003-03-13&rft.volume=46&rft.issue=6&rft.spage=1016&rft.epage=1030&rft.pages=1016-1030&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm020335m&rft_dat=%3Cproquest_cross%3E73076428%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=73076428&rft_id=info:pmid/12620078&rfr_iscdi=true |