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Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists
We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved...
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| Published in: | Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (12), p.3609-3613 |
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| Main Authors: | , , , , , , , , , , , , , |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c413t-5e8cd5350454700f2fd95fd36c8fe3505072afc93fd0b71e153f1eaf01fc98a53 |
| container_end_page | 3613 |
| container_issue | 12 |
| container_start_page | 3609 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 23 |
| creator | Zhang, Jian (Ken) Li, An-Rong Yu, Ming Wang, Yingcai Zhu, Jiang Kayser, Frank Medina, Julio C. Siegler, Karen Conn, Marion Shan, Bei Grillo, Mark P. Eksterowicz, John Coward, Peter Liu, Jiwen (Jim) |
| description | We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.
We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties. |
| doi_str_mv | 10.1016/j.bmcl.2013.04.014 |
| format | article |
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We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2013.04.014</identifier><identifier>PMID: 23648181</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>agonists ; Aniline Compounds - chemical synthesis ; Aniline Compounds - chemistry ; Aniline Compounds - pharmacology ; Animals ; chemistry ; Diabetes Mellitus, Type 2 - drug therapy ; Drug Discovery ; GPR119 agonist ; Humans ; Metabolic stability ; Mice ; Models, Molecular ; pharmacokinetics ; Receptors, G-Protein-Coupled - agonists ; Receptors, G-Protein-Coupled - chemistry ; SAR optimization ; Structure-Activity Relationship ; Type 2 diabetes</subject><ispartof>Bioorganic & medicinal chemistry letters, 2013-06, Vol.23 (12), p.3609-3613</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-5e8cd5350454700f2fd95fd36c8fe3505072afc93fd0b71e153f1eaf01fc98a53</citedby><cites>FETCH-LOGICAL-c413t-5e8cd5350454700f2fd95fd36c8fe3505072afc93fd0b71e153f1eaf01fc98a53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23648181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jian (Ken)</creatorcontrib><creatorcontrib>Li, An-Rong</creatorcontrib><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Wang, Yingcai</creatorcontrib><creatorcontrib>Zhu, Jiang</creatorcontrib><creatorcontrib>Kayser, Frank</creatorcontrib><creatorcontrib>Medina, Julio C.</creatorcontrib><creatorcontrib>Siegler, Karen</creatorcontrib><creatorcontrib>Conn, Marion</creatorcontrib><creatorcontrib>Shan, Bei</creatorcontrib><creatorcontrib>Grillo, Mark P.</creatorcontrib><creatorcontrib>Eksterowicz, John</creatorcontrib><creatorcontrib>Coward, Peter</creatorcontrib><creatorcontrib>Liu, Jiwen (Jim)</creatorcontrib><title>Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.
We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.</description><subject>agonists</subject><subject>Aniline Compounds - chemical synthesis</subject><subject>Aniline Compounds - chemistry</subject><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>chemistry</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Drug Discovery</subject><subject>GPR119 agonist</subject><subject>Humans</subject><subject>Metabolic stability</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>pharmacokinetics</subject><subject>Receptors, G-Protein-Coupled - agonists</subject><subject>Receptors, G-Protein-Coupled - chemistry</subject><subject>SAR optimization</subject><subject>Structure-Activity Relationship</subject><subject>Type 2 diabetes</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkU1rVDEUhoModlr9Ay40y3Zxb0--7ge4KVWrUKioBXchk4-SITcZkzvF219vhqkupavA4TkvJ--D0BsCLQHSnW_a9aRDS4GwFngLhD9DK8I73jAO4jlawdhBM4z85xE6LmUDlQDOX6Ijyjo-kIGskPzgi073Ni9YRYPTdvaTf1CzTxEnh1VeQtkFl-ISMGtOt0v2xseGNktIv5czFX3w0RasCo41JuCrr98IGbG6S9GXubxCL5wKxb5-fE_Q7aePPy4_N9c3V18uL64bzQmbG2EHbQQTwAXvARx1ZhTOsE4PztaxgJ4qp0fmDKx7YolgjljlgNThoAQ7QaeH3G1Ov3a2zHKqH7MhqGjTrkjCegqCUzI8ARWM910HtKL0gOqcSsnWyW32Uy1FEpB7B3Ij9w7k3oEELmvDdentY_5uPVnzb-Vv6RV4dwCcSlLdZV_k7feaIKogRqujSrw_ELZWdu9tlkV7G7U1Pls9S5P8_y74AyDBoHc</recordid><startdate>20130615</startdate><enddate>20130615</enddate><creator>Zhang, Jian (Ken)</creator><creator>Li, An-Rong</creator><creator>Yu, Ming</creator><creator>Wang, Yingcai</creator><creator>Zhu, Jiang</creator><creator>Kayser, Frank</creator><creator>Medina, Julio C.</creator><creator>Siegler, Karen</creator><creator>Conn, Marion</creator><creator>Shan, Bei</creator><creator>Grillo, Mark P.</creator><creator>Eksterowicz, John</creator><creator>Coward, Peter</creator><creator>Liu, Jiwen (Jim)</creator><general>Elsevier Ltd</general><scope>FBQ</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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20130615</creationdate><title>Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists</title><author>Zhang, Jian (Ken) ; Li, An-Rong ; Yu, Ming ; Wang, Yingcai ; Zhu, Jiang ; Kayser, Frank ; Medina, Julio C. ; Siegler, Karen ; Conn, Marion ; Shan, Bei ; Grillo, Mark P. ; Eksterowicz, John ; Coward, Peter ; Liu, Jiwen (Jim)</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-5e8cd5350454700f2fd95fd36c8fe3505072afc93fd0b71e153f1eaf01fc98a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>agonists</topic><topic>Aniline Compounds - chemical synthesis</topic><topic>Aniline Compounds - chemistry</topic><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>chemistry</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Drug Discovery</topic><topic>GPR119 agonist</topic><topic>Humans</topic><topic>Metabolic stability</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>pharmacokinetics</topic><topic>Receptors, G-Protein-Coupled - agonists</topic><topic>Receptors, G-Protein-Coupled - chemistry</topic><topic>SAR optimization</topic><topic>Structure-Activity Relationship</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jian (Ken)</creatorcontrib><creatorcontrib>Li, An-Rong</creatorcontrib><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Wang, Yingcai</creatorcontrib><creatorcontrib>Zhu, Jiang</creatorcontrib><creatorcontrib>Kayser, Frank</creatorcontrib><creatorcontrib>Medina, Julio C.</creatorcontrib><creatorcontrib>Siegler, Karen</creatorcontrib><creatorcontrib>Conn, Marion</creatorcontrib><creatorcontrib>Shan, Bei</creatorcontrib><creatorcontrib>Grillo, Mark P.</creatorcontrib><creatorcontrib>Eksterowicz, John</creatorcontrib><creatorcontrib>Coward, Peter</creatorcontrib><creatorcontrib>Liu, Jiwen (Jim)</creatorcontrib><collection>AGRIS</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><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 letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jian (Ken)</au><au>Li, An-Rong</au><au>Yu, Ming</au><au>Wang, Yingcai</au><au>Zhu, Jiang</au><au>Kayser, Frank</au><au>Medina, Julio C.</au><au>Siegler, Karen</au><au>Conn, Marion</au><au>Shan, Bei</au><au>Grillo, Mark P.</au><au>Eksterowicz, John</au><au>Coward, Peter</au><au>Liu, Jiwen (Jim)</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2013-06-15</date><risdate>2013</risdate><volume>23</volume><issue>12</issue><spage>3609</spage><epage>3613</epage><pages>3609-3613</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.
We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>23648181</pmid><doi>10.1016/j.bmcl.2013.04.014</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2013-06, Vol.23 (12), p.3609-3613 |
| issn | 0960-894X 1464-3405 |
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| source | ScienceDirect Freedom Collection |
| subjects | agonists Aniline Compounds - chemical synthesis Aniline Compounds - chemistry Aniline Compounds - pharmacology Animals chemistry Diabetes Mellitus, Type 2 - drug therapy Drug Discovery GPR119 agonist Humans Metabolic stability Mice Models, Molecular pharmacokinetics Receptors, G-Protein-Coupled - agonists Receptors, G-Protein-Coupled - chemistry SAR optimization Structure-Activity Relationship Type 2 diabetes |
| title | Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists |
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