Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists: Design, Synthesis, Structural Biology, and Molecular Docking Studies
A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were impo...
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| Veröffentlicht in: | Journal of medicinal chemistry 2006-02, Vol.49 (3), p.1212-1216 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 49 |
| creator | Mahindroo, Neeraj Wang, Chiung-Chiu Liao, Chun-Chen Huang, Chien-Fu Lu, I-Lin Lien, Tzu-Wen Peng, Yi-Huei Huang, Wei-Jan Lin, Ying-Ting Hsu, Ming-Chen Lin, Chia-Hui Tsai, Chia-Hua Hsu, John T.-A Chen, Xin Lyu, Ping-Chiang Chao, Yu-Sheng Wu, Su-Ying Hsieh, Hsing-Pang |
| description | A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity. |
| doi_str_mv | 10.1021/jm0510373 |
| format | Article |
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The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm0510373</identifier><identifier>PMID: 16451087</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Binding Sites ; Biological and medical sciences ; Crystallography, X-Ray ; Drug Design ; Hydrophobic and Hydrophilic Interactions ; Indoleacetic Acids - chemical synthesis ; Indoleacetic Acids - chemistry ; Ligands ; Medical sciences ; Miscellaneous ; Models, Molecular ; Naphthalenes - chemical synthesis ; Naphthalenes - chemistry ; Pharmacology. Drug treatments ; PPAR gamma - agonists ; PPAR gamma - chemistry ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 2006-02, Vol.49 (3), p.1212-1216</ispartof><rights>Copyright © 2006 American Chemical Society</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a447t-68e25a1c5995a477fb9d24a8b2fa28d4510547799e51a640ba3b498283be425e3</citedby><cites>FETCH-LOGICAL-a447t-68e25a1c5995a477fb9d24a8b2fa28d4510547799e51a640ba3b498283be425e3</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/jm0510373$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm0510373$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17496507$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16451087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mahindroo, Neeraj</creatorcontrib><creatorcontrib>Wang, Chiung-Chiu</creatorcontrib><creatorcontrib>Liao, Chun-Chen</creatorcontrib><creatorcontrib>Huang, Chien-Fu</creatorcontrib><creatorcontrib>Lu, I-Lin</creatorcontrib><creatorcontrib>Lien, Tzu-Wen</creatorcontrib><creatorcontrib>Peng, Yi-Huei</creatorcontrib><creatorcontrib>Huang, Wei-Jan</creatorcontrib><creatorcontrib>Lin, Ying-Ting</creatorcontrib><creatorcontrib>Hsu, Ming-Chen</creatorcontrib><creatorcontrib>Lin, Chia-Hui</creatorcontrib><creatorcontrib>Tsai, Chia-Hua</creatorcontrib><creatorcontrib>Hsu, John T.-A</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Lyu, Ping-Chiang</creatorcontrib><creatorcontrib>Chao, Yu-Sheng</creatorcontrib><creatorcontrib>Wu, Su-Ying</creatorcontrib><creatorcontrib>Hsieh, Hsing-Pang</creatorcontrib><title>Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists: Design, Synthesis, Structural Biology, and Molecular Docking Studies</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.</description><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Crystallography, X-Ray</subject><subject>Drug Design</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Indoleacetic Acids - chemical synthesis</subject><subject>Indoleacetic Acids - chemistry</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Models, Molecular</subject><subject>Naphthalenes - chemical synthesis</subject><subject>Naphthalenes - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>PPAR gamma - agonists</subject><subject>PPAR gamma - chemistry</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1uEzEQxy0EoqFw4AWQLyAhdcGf-9FbSPkoakXUFonbatY7G5w662DvoubGlSfg_XgSHCVqLhxGMxr_5q_xfwh5ztkbzgR_u1wxzZks5AMy4VqwTJVMPSQTxoTIRC7kEXkS45IxJrmQj8kRz1UaKIsJ-XPet95lPNs4OjU4WJOSbSOFSOcY_J2NfoV0HryzHQYYfMimZrA_YcCWXqHBdWrR6cL3Ng7x9O-v3_QMo130J_R60w_fUx1TOYTRDGMAR99Z7_xic0Khb-mld2hGB4GeeXNr-0Uix9ZifEoedeAiPtvnY_L1w_ub2afs4svH89n0IgOliiHLSxQauNFVpUEVRddUrVBQNqIDUbbbX-rUrirUHHLFGpCNqkpRygaV0CiPyaud7jr4HyPGoV7ZaNA56NGPsc6LXCQVmcDXO9AEH2PArl4Hu4KwqTmrt1eo76-Q2Bd70bFZYXsg97Yn4OUegGjAdQF6Y-OBK1SVa7blsh2XvMW7-3cIt2kxWej6Zn5dX13O1LcU9eeDLphYL_0Y-uTdfxb8B56cq0g</recordid><startdate>20060209</startdate><enddate>20060209</enddate><creator>Mahindroo, Neeraj</creator><creator>Wang, Chiung-Chiu</creator><creator>Liao, Chun-Chen</creator><creator>Huang, Chien-Fu</creator><creator>Lu, I-Lin</creator><creator>Lien, Tzu-Wen</creator><creator>Peng, Yi-Huei</creator><creator>Huang, Wei-Jan</creator><creator>Lin, Ying-Ting</creator><creator>Hsu, Ming-Chen</creator><creator>Lin, Chia-Hui</creator><creator>Tsai, Chia-Hua</creator><creator>Hsu, John T.-A</creator><creator>Chen, Xin</creator><creator>Lyu, Ping-Chiang</creator><creator>Chao, Yu-Sheng</creator><creator>Wu, Su-Ying</creator><creator>Hsieh, Hsing-Pang</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>20060209</creationdate><title>Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists: Design, Synthesis, Structural Biology, and Molecular Docking Studies</title><author>Mahindroo, Neeraj ; Wang, Chiung-Chiu ; Liao, Chun-Chen ; Huang, Chien-Fu ; Lu, I-Lin ; Lien, Tzu-Wen ; Peng, Yi-Huei ; Huang, Wei-Jan ; Lin, Ying-Ting ; Hsu, Ming-Chen ; Lin, Chia-Hui ; Tsai, Chia-Hua ; Hsu, John T.-A ; Chen, Xin ; Lyu, Ping-Chiang ; Chao, Yu-Sheng ; Wu, Su-Ying ; Hsieh, Hsing-Pang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a447t-68e25a1c5995a477fb9d24a8b2fa28d4510547799e51a640ba3b498283be425e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Crystallography, X-Ray</topic><topic>Drug Design</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Indoleacetic Acids - chemical synthesis</topic><topic>Indoleacetic Acids - chemistry</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Models, Molecular</topic><topic>Naphthalenes - chemical synthesis</topic><topic>Naphthalenes - chemistry</topic><topic>Pharmacology. 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Med. Chem</addtitle><date>2006-02-09</date><risdate>2006</risdate><volume>49</volume><issue>3</issue><spage>1212</spage><epage>1216</epage><pages>1212-1216</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A series of novel indole-based PPAR agonists is described leading to discovery of 10k, a highly potent PPAR pan-agonist. The structural biology and molecular docking studies revealed that the distances between the acidic group and the linker, when a ligand was complexed with PPARγ protein, were important for the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic interaction with the PPARγ protein resulting in potent activity.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>16451087</pmid><doi>10.1021/jm0510373</doi><tpages>5</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2006-02, Vol.49 (3), p.1212-1216 |
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| subjects | Binding Sites Biological and medical sciences Crystallography, X-Ray Drug Design Hydrophobic and Hydrophilic Interactions Indoleacetic Acids - chemical synthesis Indoleacetic Acids - chemistry Ligands Medical sciences Miscellaneous Models, Molecular Naphthalenes - chemical synthesis Naphthalenes - chemistry Pharmacology. Drug treatments PPAR gamma - agonists PPAR gamma - chemistry Structure-Activity Relationship |
| title | Indol-1-yl Acetic Acids as Peroxisome Proliferator-Activated Receptor Agonists: Design, Synthesis, Structural Biology, and Molecular Docking Studies |
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