In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist
To investigate the anorectic potential of NPY5 receptor antagonists, we have profiled the in vitro and in vivo properties of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt (1). This compound was found to have excellent NPY5 receptor affinity and selectivi...
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| Veröffentlicht in: | Journal of medicinal chemistry 2003-02, Vol.46 (5), p.670-673 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 46 |
| creator | Elliott, Richard L Oliver, Robert M Hammond, Marlys Patterson, Terrell A She, Li Hargrove, Diane M Martin, Kelly A Maurer, Tristan S Kalvass, J Cory Morgan, Bradley P DaSilva-Jardine, Paul A Stevenson, Ralph W Mack, Christine M Cassella, James V |
| description | To investigate the anorectic potential of NPY5 receptor antagonists, we have profiled the in vitro and in vivo properties of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt (1). This compound was found to have excellent NPY5 receptor affinity and selectivity, potent functional antagonism, and good peripheral and central nervous system exposure in rats. This compound attenuated bovine pancreatic polypeptide induced food intake in rats but failed to demonstrate anorectic activity in rodent natural feeding models. |
| doi_str_mv | 10.1021/jm025584p |
| format | Article |
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This compound was found to have excellent NPY5 receptor affinity and selectivity, potent functional antagonism, and good peripheral and central nervous system exposure in rats. This compound attenuated bovine pancreatic polypeptide induced food intake in rats but failed to demonstrate anorectic activity in rodent natural feeding models.</description><identifier>ISSN: 0022-2623</identifier><identifier>DOI: 10.1021/jm025584p</identifier><identifier>PMID: 12593645</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Brain - metabolism ; Calcium - metabolism ; Cattle ; Cerebrospinal Fluid - metabolism ; Eating - drug effects ; Humans ; Imidazoles - chemical synthesis ; Imidazoles - pharmacokinetics ; Imidazoles - pharmacology ; In Vitro Techniques ; Male ; Nitriles - chemical synthesis ; Nitriles - pharmacokinetics ; Nitriles - pharmacology ; Pancreatic Polypeptide - pharmacology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Neuropeptide Y - antagonists & inhibitors ; Receptors, Neuropeptide Y - metabolism ; Tissue Distribution ; Tumor Cells, Cultured</subject><ispartof>Journal of medicinal chemistry, 2003-02, Vol.46 (5), p.670-673</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12593645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elliott, Richard L</creatorcontrib><creatorcontrib>Oliver, Robert M</creatorcontrib><creatorcontrib>Hammond, Marlys</creatorcontrib><creatorcontrib>Patterson, Terrell A</creatorcontrib><creatorcontrib>She, Li</creatorcontrib><creatorcontrib>Hargrove, Diane M</creatorcontrib><creatorcontrib>Martin, Kelly A</creatorcontrib><creatorcontrib>Maurer, Tristan S</creatorcontrib><creatorcontrib>Kalvass, J Cory</creatorcontrib><creatorcontrib>Morgan, Bradley P</creatorcontrib><creatorcontrib>DaSilva-Jardine, Paul A</creatorcontrib><creatorcontrib>Stevenson, Ralph W</creatorcontrib><creatorcontrib>Mack, Christine M</creatorcontrib><creatorcontrib>Cassella, James V</creatorcontrib><title>In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist</title><title>Journal of medicinal chemistry</title><addtitle>J Med Chem</addtitle><description>To investigate the anorectic potential of NPY5 receptor antagonists, we have profiled the in vitro and in vivo properties of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt (1). This compound was found to have excellent NPY5 receptor affinity and selectivity, potent functional antagonism, and good peripheral and central nervous system exposure in rats. This compound attenuated bovine pancreatic polypeptide induced food intake in rats but failed to demonstrate anorectic activity in rodent natural feeding models.</description><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Calcium - metabolism</subject><subject>Cattle</subject><subject>Cerebrospinal Fluid - metabolism</subject><subject>Eating - drug effects</subject><subject>Humans</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - pharmacokinetics</subject><subject>Imidazoles - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Nitriles - chemical synthesis</subject><subject>Nitriles - pharmacokinetics</subject><subject>Nitriles - pharmacology</subject><subject>Pancreatic Polypeptide - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rats, Wistar</subject><subject>Receptors, Neuropeptide Y - antagonists & inhibitors</subject><subject>Receptors, Neuropeptide Y - metabolism</subject><subject>Tissue Distribution</subject><subject>Tumor Cells, Cultured</subject><issn>0022-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1UE1P3DAQ9aEVC9se-geQTwikuvgjjjdHhKAgrdoe6AGt0MpxJqyREwfbWZH9X_w_DN1e3tPMm3lvNAh9Y_QHo5ydP3WUS7kohk_okFLOCS-5mKGjGJ8opYJxcYBmjMtKlIU8RK-3Pd7aFDzWfYPte7H12Gx00CZBsDudrO-xb7EgK05WJTnlJAuJ1GPyLxOkTcazYQq2sT0RZHIPhN0Q29lG77wjxXunhn7n-xxjHeDN1ARvNs7nFcBRu_Qdazz4BH36uCKCA5PsFvCvP_cSBzAwJB-ylvRjtonpC_rcahfh657n6O_11d3lDVn-_nl7ebEkAxNVIovaMKkE1aoy0lBVS6l40QAvq5aXpq5NJaXIrBet1ka3kpWNrBrFK6UKpsQcnfzzHYJ_HiGmdWejAed0D36M6-wtVJlhjo73g2PdQbMegu10mNb_Hy3eAM_jgAc</recordid><startdate>20030227</startdate><enddate>20030227</enddate><creator>Elliott, Richard L</creator><creator>Oliver, Robert M</creator><creator>Hammond, Marlys</creator><creator>Patterson, Terrell A</creator><creator>She, Li</creator><creator>Hargrove, Diane M</creator><creator>Martin, Kelly A</creator><creator>Maurer, Tristan S</creator><creator>Kalvass, J Cory</creator><creator>Morgan, Bradley P</creator><creator>DaSilva-Jardine, Paul A</creator><creator>Stevenson, Ralph W</creator><creator>Mack, Christine M</creator><creator>Cassella, James V</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030227</creationdate><title>In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist</title><author>Elliott, Richard L ; Oliver, Robert M ; Hammond, Marlys ; Patterson, Terrell A ; She, Li ; Hargrove, Diane M ; Martin, Kelly A ; Maurer, Tristan S ; Kalvass, J Cory ; Morgan, Bradley P ; DaSilva-Jardine, Paul A ; Stevenson, Ralph W ; Mack, Christine M ; Cassella, James V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p139t-8bc15730a79c5c07b55724de269f26cbbc9553cbba8faacaf516d59d729774173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Calcium - metabolism</topic><topic>Cattle</topic><topic>Cerebrospinal Fluid - metabolism</topic><topic>Eating - drug effects</topic><topic>Humans</topic><topic>Imidazoles - chemical synthesis</topic><topic>Imidazoles - pharmacokinetics</topic><topic>Imidazoles - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Nitriles - chemical synthesis</topic><topic>Nitriles - pharmacokinetics</topic><topic>Nitriles - pharmacology</topic><topic>Pancreatic Polypeptide - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rats, Wistar</topic><topic>Receptors, Neuropeptide Y - antagonists & inhibitors</topic><topic>Receptors, Neuropeptide Y - metabolism</topic><topic>Tissue Distribution</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elliott, Richard L</creatorcontrib><creatorcontrib>Oliver, Robert M</creatorcontrib><creatorcontrib>Hammond, Marlys</creatorcontrib><creatorcontrib>Patterson, Terrell A</creatorcontrib><creatorcontrib>She, Li</creatorcontrib><creatorcontrib>Hargrove, Diane M</creatorcontrib><creatorcontrib>Martin, Kelly A</creatorcontrib><creatorcontrib>Maurer, Tristan S</creatorcontrib><creatorcontrib>Kalvass, J Cory</creatorcontrib><creatorcontrib>Morgan, Bradley P</creatorcontrib><creatorcontrib>DaSilva-Jardine, Paul A</creatorcontrib><creatorcontrib>Stevenson, Ralph W</creatorcontrib><creatorcontrib>Mack, Christine M</creatorcontrib><creatorcontrib>Cassella, James V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elliott, Richard L</au><au>Oliver, Robert M</au><au>Hammond, Marlys</au><au>Patterson, Terrell A</au><au>She, Li</au><au>Hargrove, Diane M</au><au>Martin, Kelly A</au><au>Maurer, Tristan S</au><au>Kalvass, J Cory</au><au>Morgan, Bradley P</au><au>DaSilva-Jardine, Paul A</au><au>Stevenson, Ralph W</au><au>Mack, Christine M</au><au>Cassella, James V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J Med Chem</addtitle><date>2003-02-27</date><risdate>2003</risdate><volume>46</volume><issue>5</issue><spage>670</spage><epage>673</epage><pages>670-673</pages><issn>0022-2623</issn><abstract>To investigate the anorectic potential of NPY5 receptor antagonists, we have profiled the in vitro and in vivo properties of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt (1). This compound was found to have excellent NPY5 receptor affinity and selectivity, potent functional antagonism, and good peripheral and central nervous system exposure in rats. This compound attenuated bovine pancreatic polypeptide induced food intake in rats but failed to demonstrate anorectic activity in rodent natural feeding models.</abstract><cop>United States</cop><pmid>12593645</pmid><doi>10.1021/jm025584p</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Brain - metabolism Calcium - metabolism Cattle Cerebrospinal Fluid - metabolism Eating - drug effects Humans Imidazoles - chemical synthesis Imidazoles - pharmacokinetics Imidazoles - pharmacology In Vitro Techniques Male Nitriles - chemical synthesis Nitriles - pharmacokinetics Nitriles - pharmacology Pancreatic Polypeptide - pharmacology Rats Rats, Sprague-Dawley Rats, Wistar Receptors, Neuropeptide Y - antagonists & inhibitors Receptors, Neuropeptide Y - metabolism Tissue Distribution Tumor Cells, Cultured |
| title | In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist |
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