Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity
Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as 10 that are devoid of cytochr...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-11, Vol.14 (22), p.5481-5484 |
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| container_end_page | 5484 |
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| container_issue | 22 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 14 |
| creator | Smith, Nicholas D. Poon, Steve F. Huang, Dehua Green, Mitchell King, Christopher Tehrani, Lida Roppe, Jeffrey R. Chung, Janice Chapman, Deborah P. Cramer, Merryl Cosford, Nicholas D.P. |
| description | Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as
10 that are devoid of cytochrome P450 inhibitory activity.
Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as (
10) that are devoid of cytochrome P450 inhibitory activity. |
| doi_str_mv | 10.1016/j.bmcl.2004.09.018 |
| format | Article |
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10 that are devoid of cytochrome P450 inhibitory activity.
Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as (
10) that are devoid of cytochrome P450 inhibitory activity.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2004.09.018</identifier><identifier>PMID: 15482908</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Administration, Oral ; Animals ; Antagonist ; Anti-Anxiety Agents - chemical synthesis ; Anti-Anxiety Agents - chemistry ; Anti-Anxiety Agents - pharmacokinetics ; Biological and medical sciences ; Biological Availability ; Cytochrome P-450 CYP1A2 Inhibitors ; Cytochrome P450 1A2 ; Glutamatergic system (aspartate and other excitatory aminoacids) ; Medical sciences ; Metabotropic glutamate ; Molecular Structure ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate - antagonists & inhibitors ; Structure-Activity Relationship ; Tetrazole ; Tetrazoles - chemical synthesis ; Tetrazoles - chemistry ; Tetrazoles - pharmacokinetics</subject><ispartof>Bioorganic & medicinal chemistry letters, 2004-11, Vol.14 (22), p.5481-5484</ispartof><rights>2004 Elsevier Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-f528782d8de3a63b187542509ad0b76d63862216d92fca587907b716af8bd5793</citedby><cites>FETCH-LOGICAL-c382t-f528782d8de3a63b187542509ad0b76d63862216d92fca587907b716af8bd5793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X04011308$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16202550$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15482908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smith, Nicholas D.</creatorcontrib><creatorcontrib>Poon, Steve F.</creatorcontrib><creatorcontrib>Huang, Dehua</creatorcontrib><creatorcontrib>Green, Mitchell</creatorcontrib><creatorcontrib>King, Christopher</creatorcontrib><creatorcontrib>Tehrani, Lida</creatorcontrib><creatorcontrib>Roppe, Jeffrey R.</creatorcontrib><creatorcontrib>Chung, Janice</creatorcontrib><creatorcontrib>Chapman, Deborah P.</creatorcontrib><creatorcontrib>Cramer, Merryl</creatorcontrib><creatorcontrib>Cosford, Nicholas D.P.</creatorcontrib><title>Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as
10 that are devoid of cytochrome P450 inhibitory activity.
Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as (
10) that are devoid of cytochrome P450 inhibitory activity.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antagonist</subject><subject>Anti-Anxiety Agents - chemical synthesis</subject><subject>Anti-Anxiety Agents - chemistry</subject><subject>Anti-Anxiety Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Cytochrome P-450 CYP1A2 Inhibitors</subject><subject>Cytochrome P450 1A2</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>Medical sciences</subject><subject>Metabotropic glutamate</subject><subject>Molecular Structure</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Metabotropic Glutamate 5</subject><subject>Receptors, Metabotropic Glutamate - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><subject>Tetrazole</subject><subject>Tetrazoles - chemical synthesis</subject><subject>Tetrazoles - chemistry</subject><subject>Tetrazoles - pharmacokinetics</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-L1DAYh4so7rr6BTxILorCzpikSZqCl2XVVVjQg4K3kD9vZzKkTTdJB_qZ_JK2zMDePAWS5_fm5fdU1WuCtwQT8fGwNb0NW4ox2-J2i4l8Ul0SJtimZpg_rS5xK_BGtuzPRfUi5wPGhGHGnlcXhDNJWywvq7-ffbbxCGlGsUN7v9uHGY2xwFCuUYYAtvgjXKOYdFhejI_6qH3QJiyXPRRtYklx9BbtwlR0rwugPJkyj4A4et_fhYl_QAksjCUmpIeid3HwuWTk4Bi9W7-1c4l2n2IP6CfjGJEbivyw98YvmRnpdQdf5pfVs06HDK_O51X1--uXX7ffNvc_7r7f3txvbC1p2XScykZSJx3UWtSGyIYzynGrHTaNcKKWglIiXEs7q7lsWtyYhgjdSeN409ZX1bvT3DHFhwlyUf1SEoSgB4hTVkK0DcFsBekJtCnmnKBTY_K9TrMiWK2K1EGtitSqSOFWLYqW0Jvz9Mn04B4jZycL8PYM6Gx16JIerM-PnKCYco4X7tOJg6WLo4eksvUwWHB-6bsoF_3_9vgHFsixew</recordid><startdate>20041115</startdate><enddate>20041115</enddate><creator>Smith, Nicholas D.</creator><creator>Poon, Steve F.</creator><creator>Huang, Dehua</creator><creator>Green, Mitchell</creator><creator>King, Christopher</creator><creator>Tehrani, Lida</creator><creator>Roppe, Jeffrey R.</creator><creator>Chung, Janice</creator><creator>Chapman, Deborah P.</creator><creator>Cramer, Merryl</creator><creator>Cosford, Nicholas D.P.</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>20041115</creationdate><title>Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity</title><author>Smith, Nicholas D. ; Poon, Steve F. ; Huang, Dehua ; Green, Mitchell ; King, Christopher ; Tehrani, Lida ; Roppe, Jeffrey R. ; Chung, Janice ; Chapman, Deborah P. ; Cramer, Merryl ; Cosford, Nicholas D.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-f528782d8de3a63b187542509ad0b76d63862216d92fca587907b716af8bd5793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antagonist</topic><topic>Anti-Anxiety Agents - chemical synthesis</topic><topic>Anti-Anxiety Agents - chemistry</topic><topic>Anti-Anxiety Agents - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Cytochrome P-450 CYP1A2 Inhibitors</topic><topic>Cytochrome P450 1A2</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>Medical sciences</topic><topic>Metabotropic glutamate</topic><topic>Molecular Structure</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Metabotropic Glutamate 5</topic><topic>Receptors, Metabotropic Glutamate - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><topic>Tetrazole</topic><topic>Tetrazoles - chemical synthesis</topic><topic>Tetrazoles - chemistry</topic><topic>Tetrazoles - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Nicholas D.</creatorcontrib><creatorcontrib>Poon, Steve F.</creatorcontrib><creatorcontrib>Huang, Dehua</creatorcontrib><creatorcontrib>Green, Mitchell</creatorcontrib><creatorcontrib>King, Christopher</creatorcontrib><creatorcontrib>Tehrani, Lida</creatorcontrib><creatorcontrib>Roppe, Jeffrey R.</creatorcontrib><creatorcontrib>Chung, Janice</creatorcontrib><creatorcontrib>Chapman, Deborah P.</creatorcontrib><creatorcontrib>Cramer, Merryl</creatorcontrib><creatorcontrib>Cosford, Nicholas D.P.</creatorcontrib><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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Nicholas D.</au><au>Poon, Steve F.</au><au>Huang, Dehua</au><au>Green, Mitchell</au><au>King, Christopher</au><au>Tehrani, Lida</au><au>Roppe, Jeffrey R.</au><au>Chung, Janice</au><au>Chapman, Deborah P.</au><au>Cramer, Merryl</au><au>Cosford, Nicholas D.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2004-11-15</date><risdate>2004</risdate><volume>14</volume><issue>22</issue><spage>5481</spage><epage>5484</epage><pages>5481-5484</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as
10 that are devoid of cytochrome P450 inhibitory activity.
Structure–activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as (
10) that are devoid of cytochrome P450 inhibitory activity.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15482908</pmid><doi>10.1016/j.bmcl.2004.09.018</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2004-11, Vol.14 (22), p.5481-5484 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Administration, Oral Animals Antagonist Anti-Anxiety Agents - chemical synthesis Anti-Anxiety Agents - chemistry Anti-Anxiety Agents - pharmacokinetics Biological and medical sciences Biological Availability Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P450 1A2 Glutamatergic system (aspartate and other excitatory aminoacids) Medical sciences Metabotropic glutamate Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - antagonists & inhibitors Structure-Activity Relationship Tetrazole Tetrazoles - chemical synthesis Tetrazoles - chemistry Tetrazoles - pharmacokinetics |
| title | Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity |
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