Bioorganic & medicinal chemistry letters, 2012-12, Vol.22 (23), p.7223-7226
2012
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Details
- Autor(en) / Beteiligte
- Titel
- Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2012-12, Vol.22 (23), p.7223-7226
- Ort / Verlag
- Amsterdam: Elsevier Ltd
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1=10nM). 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2012.09.048Titel-ID: cdi_proquest_miscellaneous_1272725255
- Format
- –
- Schlagworte
- Administration, Oral, Animals, Antagonists, Biological and medical sciences, chemistry, Chronic Pain - drug therapy, Disease Models, Animal, glutamic acid, Glutamic acid receptors (metabotropic), Heterocyclic Compounds, 3-Ring - chemical synthesis, Heterocyclic Compounds, 3-Ring - chemistry, Heterocyclic Compounds, 3-Ring - therapeutic use, high-throughput screening, Humans, Medical sciences, nerve tissue, oral exposure, Pain, Pharmacokinetics, Pharmacology. Drug treatments, Pyrimidinones - chemical synthesis, Pyrimidinones - chemistry, Pyrimidinones - therapeutic use, Rats, Receptors, Metabotropic Glutamate - antagonists & inhibitors, Receptors, Metabotropic Glutamate - metabolism, screening, Spinal nerves, Structure-Activity Relationship, Thiophenes - chemical synthesis, Thiophenes - chemistry, Thiophenes - therapeutic use