Synthesis and biological evaluation of 7,8,9,10-tetrahydroimidazo[1,2-c]pyrido[3,4-e]pyrimdin-5(6H)-ones as functionally selective ligands of the benzodiazepine receptor site on the GABA(A) receptor
| Autor: | John F. Tallman, Geoff White, Matt Crago, Lu Marshall, James V. Cassella, Pamela Albaugh, James Gregory, Dorothy W. Gallagher, Hutchison Alan J, Phil C. Ross |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.drug_class Stereochemistry Allosteric regulation Pyrimidinones In Vitro Techniques Motor Activity Ligands Chemical synthesis Partial agonist Binding Competitive Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship Xenopus laevis In vivo Drug Discovery Functional selectivity medicine Animals Receptor GABA Agonists Cerebral Cortex Benzodiazepine Chemistry GABAA receptor Imidazoles Receptors GABA-A Rats Electrophysiology Oocytes Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry. 45(23) |
| ISSN: | 0022-2623 |
| Popis: | Benzodiazepines are allosteric modulators of the GABA(A) receptor. The traditionally prescribed benzodiazepines are nonselective and suffer from numerous side effects. Upon the identification of receptor subtypes, we set out to discover selective agents with the anticipation that these agents would have superior therapeutic potential. Herein, we describe the synthesis and biological evaluation of substituted 7,8,9,10-tetrahydroimidazo[1,2-c]pyrido[3,4-e]pyrimidin-5(6H)-ones and disclose that these compounds exhibit functional selectivity at the benzodiazepine receptor of GABA(A) receptor subtypes. The alpha(2)/alpha(3)-selective partial agonist 42 exhibited potent in vivo activity. |
| Databáze: | OpenAIRE |
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