Discovery of GlyT1 inhibitors with improved pharmacokinetic properties
Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is dis...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-03, Vol.19 (5), p.1492-1495 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Wolkenberg, Scott E. Zhao, Zhijian Wisnoski, David D. Leister, William H. O’Brien, Julie Lemaire, Wei Williams, David L. Jacobson, Marlene A. Sur, Cyrille Kinney, Gene G. Pettibone, Doug J. Tiller, Philip R. Smith, Sheri Gibson, Christopher Ma, Bennett K. Polsky-Fisher, Stacey L. Lindsley, Craig W. Hartman, George D. |
| description | Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed. |
| doi_str_mv | 10.1016/j.bmcl.2009.01.015 |
| format | Article |
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The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed.</description><subject>Animals</subject><subject>Cassette dosing</subject><subject>Dogs</subject><subject>Drug Discovery - methods</subject><subject>Glycine - biosynthesis</subject><subject>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</subject><subject>Glycine Plasma Membrane Transport Proteins - metabolism</subject><subject>GlyT1</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>N-Methylaspartate - chemistry</subject><subject>N-Methylaspartate - pharmacology</subject><subject>NMDA pharmacokinetics</subject><subject>Piperidines - administration & dosage</subject><subject>Piperidines - chemical synthesis</subject><subject>Piperidines - pharmacokinetics</subject><subject>Rats</subject><subject>Schizophrenia</subject><subject>Substrate Specificity</subject><subject>Sulfonamides - chemical synthesis</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1Lw0AQhhdRbK3-AQ-Sk7fEmXR3k4AXUVuFgpcK3pZkM6Fb8-VuWum_d0sL3hQGFoZn33l5GLtGiBBQ3q2jotF1FANkEaAfccLGyCUPpxzEKRtDJiFMM_4xYhfOrQGQA-fnbIQZpihiMWazJ-N0tyW7C7oqmNe7JQamXZnCDJ11wbcZVoFpeuuRMuhXuW1y3X2algajA7_uyQ6G3CU7q_La0dXxnbD32fPy8SVcvM1fHx8WoZ6mYvC94rgo0opzAbqqMEdRUOIra4mgi7JAngHXlCMnKUnqJE_LBAjjaZbIRE8n7PaQ609_bcgNqvH9qa7zlrqNU1JmPElS8S8YA5ciQfBgfAC17ZyzVKnemia3O4Wg9prVWu01q71mBehnn35zTN8UDZW_X45ePXB_AMjL2BqyymlDrabSWNKDKjvzV_4PnNuOfQ</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Wolkenberg, Scott E.</creator><creator>Zhao, Zhijian</creator><creator>Wisnoski, David D.</creator><creator>Leister, William H.</creator><creator>O’Brien, Julie</creator><creator>Lemaire, Wei</creator><creator>Williams, David L.</creator><creator>Jacobson, Marlene A.</creator><creator>Sur, Cyrille</creator><creator>Kinney, Gene G.</creator><creator>Pettibone, Doug J.</creator><creator>Tiller, Philip R.</creator><creator>Smith, Sheri</creator><creator>Gibson, Christopher</creator><creator>Ma, Bennett K.</creator><creator>Polsky-Fisher, Stacey L.</creator><creator>Lindsley, Craig W.</creator><creator>Hartman, George D.</creator><general>Elsevier Ltd</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090301</creationdate><title>Discovery of GlyT1 inhibitors with improved pharmacokinetic properties</title><author>Wolkenberg, Scott E. ; Zhao, Zhijian ; Wisnoski, David D. ; Leister, William H. ; O’Brien, Julie ; Lemaire, Wei ; Williams, David L. ; Jacobson, Marlene A. ; Sur, Cyrille ; Kinney, Gene G. ; Pettibone, Doug J. ; Tiller, Philip R. ; Smith, Sheri ; Gibson, Christopher ; Ma, Bennett K. ; Polsky-Fisher, Stacey L. ; Lindsley, Craig W. ; Hartman, George D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-3422bb8f4450cff1a15be7146c610cbdb14904cea14e66e6c7a8d70e1239767c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Cassette dosing</topic><topic>Dogs</topic><topic>Drug Discovery - methods</topic><topic>Glycine - biosynthesis</topic><topic>Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors</topic><topic>Glycine Plasma Membrane Transport Proteins - metabolism</topic><topic>GlyT1</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>N-Methylaspartate - chemistry</topic><topic>N-Methylaspartate - pharmacology</topic><topic>NMDA pharmacokinetics</topic><topic>Piperidines - administration & dosage</topic><topic>Piperidines - chemical synthesis</topic><topic>Piperidines - pharmacokinetics</topic><topic>Rats</topic><topic>Schizophrenia</topic><topic>Substrate Specificity</topic><topic>Sulfonamides - chemical synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wolkenberg, Scott E.</creatorcontrib><creatorcontrib>Zhao, Zhijian</creatorcontrib><creatorcontrib>Wisnoski, David D.</creatorcontrib><creatorcontrib>Leister, William H.</creatorcontrib><creatorcontrib>O’Brien, Julie</creatorcontrib><creatorcontrib>Lemaire, Wei</creatorcontrib><creatorcontrib>Williams, David L.</creatorcontrib><creatorcontrib>Jacobson, Marlene A.</creatorcontrib><creatorcontrib>Sur, Cyrille</creatorcontrib><creatorcontrib>Kinney, Gene G.</creatorcontrib><creatorcontrib>Pettibone, Doug J.</creatorcontrib><creatorcontrib>Tiller, Philip R.</creatorcontrib><creatorcontrib>Smith, Sheri</creatorcontrib><creatorcontrib>Gibson, Christopher</creatorcontrib><creatorcontrib>Ma, Bennett K.</creatorcontrib><creatorcontrib>Polsky-Fisher, Stacey L.</creatorcontrib><creatorcontrib>Lindsley, Craig W.</creatorcontrib><creatorcontrib>Hartman, George D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wolkenberg, Scott E.</au><au>Zhao, Zhijian</au><au>Wisnoski, David D.</au><au>Leister, William H.</au><au>O’Brien, Julie</au><au>Lemaire, Wei</au><au>Williams, David L.</au><au>Jacobson, Marlene A.</au><au>Sur, Cyrille</au><au>Kinney, Gene G.</au><au>Pettibone, Doug J.</au><au>Tiller, Philip R.</au><au>Smith, Sheri</au><au>Gibson, Christopher</au><au>Ma, Bennett K.</au><au>Polsky-Fisher, Stacey L.</au><au>Lindsley, Craig W.</au><au>Hartman, George D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of GlyT1 inhibitors with improved pharmacokinetic properties</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>19</volume><issue>5</issue><spage>1492</spage><epage>1495</epage><pages>1492-1495</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. 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| ispartof | Bioorganic & medicinal chemistry letters, 2009-03, Vol.19 (5), p.1492-1495 |
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| subjects | Animals Cassette dosing Dogs Drug Discovery - methods Glycine - biosynthesis Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors Glycine Plasma Membrane Transport Proteins - metabolism GlyT1 Humans Mice Mice, Inbred DBA N-Methylaspartate - chemistry N-Methylaspartate - pharmacology NMDA pharmacokinetics Piperidines - administration & dosage Piperidines - chemical synthesis Piperidines - pharmacokinetics Rats Schizophrenia Substrate Specificity Sulfonamides - chemical synthesis |
| title | Discovery of GlyT1 inhibitors with improved pharmacokinetic properties |
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