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Structure–activity relationships of novel non-competitive mGluR1 antagonists: A potential treatment for chronic pain
Weakly active ( 4) was converted into low molecular weight, high activity ( 29) using library chemistry. A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driv...
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| Published in: | Bioorganic & medicinal chemistry letters 2007-01, Vol.17 (2), p.486-490 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c384t-ada9c88291a8c18776aab862ca5e8bf8770e7cf47d0510392634f1ef279ceea63 |
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| cites | cdi_FETCH-LOGICAL-c384t-ada9c88291a8c18776aab862ca5e8bf8770e7cf47d0510392634f1ef279ceea63 |
| container_end_page | 490 |
| container_issue | 2 |
| container_start_page | 486 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 17 |
| creator | Owen, Dafydd R. Dodd, Peter G. Gayton, Simon Greener, Ben S. Harbottle, Gareth W. Mantell, Simon J. Maw, Graham N. Osborne, Simon A. Rees, Huw Ringer, Tracy J. Rodriguez-Lens, Margarita Smith, Graham F. |
| description | Weakly active (
4) was converted into low molecular weight, high activity (
29) using library chemistry.
A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability. |
| doi_str_mv | 10.1016/j.bmcl.2006.10.015 |
| format | article |
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4) was converted into low molecular weight, high activity (
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4) was converted into low molecular weight, high activity (
29) using library chemistry.
A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Binding, Competitive - drug effects</subject><subject>Biological and medical sciences</subject><subject>c log P</subject><subject>Chemical Phenomena</subject><subject>Chemistry, Physical</subject><subject>CHO Cells</subject><subject>Chronic Disease</subject><subject>Chronic pain</subject><subject>CNS</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Dose-Response Relationship, Drug</subject><subject>Glutamatergic system (aspartate and other excitatory aminoacids)</subject><subject>Glutamic Acid - pharmacology</subject><subject>Library</subject><subject>log D</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>mGluR</subject><subject>mGluR1</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pain - drug therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrazine</subject><subject>Pyrazines - chemical synthesis</subject><subject>Pyrazines - pharmacology</subject><subject>Quinoxaline</subject><subject>Rats</subject><subject>Receptors, Metabotropic Glutamate - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNp9kM-KFDEQh4Mo7uzqC3iQXNxbj0l3Jp0WL8virsKC4B_wFmqqq90M3UmbpAf25jv4hj6JGWZgb16qqB9fFcXH2Csp1lJI_Xa33k44rmshdAnWQm6esJVUWlWNEpunbCU6LSrTqR9n7DylnRBSCaWeszPZCq1MZ1Zs_zXHBfMS6e_vP4DZ7V1-4JFGyC74dO_mxMPAfdjTWKqvMEwzZVdA4tPtuHyRHHyGn8G7lNM7fsXnkMlnByPPkSBPZeBDiBzvY4GQz-D8C_ZsgDHRy1O_YN9vPny7_ljdfb79dH11V2FjVK6ghw6NqTsJBqVpWw2wNbpG2JDZDiUQ1OKg2l5spGi6WjdqkDTUbYdEoJsLdnm8O8fwa6GU7eQS0jiCp7Akq42SZiNNAesjiDGkFGmwc3QTxAcrhT3Ytjt7sG0Ptg9ZsV2WXp-uL9uJ-seVk94CvDkBkBDGIYJHlx45o7SsdVe490eOiou9o2gTOvJIvYuE2fbB_e-Pf2xPoYc</recordid><startdate>20070115</startdate><enddate>20070115</enddate><creator>Owen, Dafydd R.</creator><creator>Dodd, Peter G.</creator><creator>Gayton, Simon</creator><creator>Greener, Ben S.</creator><creator>Harbottle, Gareth W.</creator><creator>Mantell, Simon J.</creator><creator>Maw, Graham N.</creator><creator>Osborne, Simon A.</creator><creator>Rees, Huw</creator><creator>Ringer, Tracy J.</creator><creator>Rodriguez-Lens, Margarita</creator><creator>Smith, Graham F.</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>20070115</creationdate><title>Structure–activity relationships of novel non-competitive mGluR1 antagonists: A potential treatment for chronic pain</title><author>Owen, Dafydd R. ; Dodd, Peter G. ; Gayton, Simon ; Greener, Ben S. ; Harbottle, Gareth W. ; Mantell, Simon J. ; Maw, Graham N. ; Osborne, Simon A. ; Rees, Huw ; Ringer, Tracy J. ; Rodriguez-Lens, Margarita ; Smith, Graham F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-ada9c88291a8c18776aab862ca5e8bf8770e7cf47d0510392634f1ef279ceea63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Binding, Competitive - drug effects</topic><topic>Biological and medical sciences</topic><topic>c log P</topic><topic>Chemical Phenomena</topic><topic>Chemistry, Physical</topic><topic>CHO Cells</topic><topic>Chronic Disease</topic><topic>Chronic pain</topic><topic>CNS</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Dose-Response Relationship, Drug</topic><topic>Glutamatergic system (aspartate and other excitatory aminoacids)</topic><topic>Glutamic Acid - pharmacology</topic><topic>Library</topic><topic>log D</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>mGluR</topic><topic>mGluR1</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. 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| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2007-01, Vol.17 (2), p.486-490 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68418518 |
| source | ScienceDirect Freedom Collection |
| subjects | Analgesics Animals Binding, Competitive - drug effects Biological and medical sciences c log P Chemical Phenomena Chemistry, Physical CHO Cells Chronic Disease Chronic pain CNS Cricetinae Cricetulus Dose-Response Relationship, Drug Glutamatergic system (aspartate and other excitatory aminoacids) Glutamic Acid - pharmacology Library log D Medical sciences Metabolism mGluR mGluR1 Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pain - drug therapy Pharmacology. Drug treatments Pyrazine Pyrazines - chemical synthesis Pyrazines - pharmacology Quinoxaline Rats Receptors, Metabotropic Glutamate - antagonists & inhibitors Structure-Activity Relationship |
| title | Structure–activity relationships of novel non-competitive mGluR1 antagonists: A potential treatment for chronic pain |
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