Abstract |
High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 ( mGluR1=10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model.
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Authors | Stephanie Brumfield, Peter Korakas, Lisa S Silverman, Deen Tulshian, Julius J Matasi, Li Qiang, Chad E Bennett, Duane A Burnett, William J Greenlee, Chad E Knutson, Wen-Lian Wu, T K Sasikumar, Martin Domalski, Rosalia Bertorelli, Mariagrazia Grilli, Gianluca Lozza, Angelo Reggiani, Cheng Li |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 22
Issue 23
Pg. 7223-6
(Dec 01 2012)
ISSN: 1464-3405 [Electronic] England |
PMID | 23084894
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Heterocyclic Compounds, 3-Ring
- Pyrimidinones
- Receptors, Metabotropic Glutamate
- Thiophenes
- metabotropic glutamate receptor type 1
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Topics |
- Administration, Oral
- Animals
- Chronic Pain
(drug therapy)
- Disease Models, Animal
- Heterocyclic Compounds, 3-Ring
(chemical synthesis, chemistry, therapeutic use)
- Humans
- Pyrimidinones
(chemical synthesis, chemistry, therapeutic use)
- Rats
- Receptors, Metabotropic Glutamate
(antagonists & inhibitors, metabolism)
- Structure-Activity Relationship
- Thiophenes
(chemical synthesis, chemistry, therapeutic use)
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