Ligands for brain cholinergic channel receptors: synthesis and in vitro characterization of novel isoxazoles and isothiazoles as bioisosteric replacements for the pyridine ring in nicotine
| Autor: | D. S. Garvey, James T. Wasicak, Suzanne A. Lebold, David J. Anderson, Nan-Horng Lin, Ann-Marie Hettinger, George M. Carrera, Yun He, Elliott Richard L, Mark W. Holladay |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Agonist
medicine.drug_class Dopamine Pharmacology Receptors Nicotinic Ligands Nicotine Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Animals Nicotinic Agonists Receptor Acetylcholine receptor Chemistry Brain Isoxazoles Rats Thiazoles Nicotinic agonist nervous system Biochemistry Molecular Medicine Cholinergic medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 37(26) |
| ISSN: | 0022-2623 |
| Popis: | Ligands which activate neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential approach for the palliative treatment for the symptoms of memory loss associated with Alzheimer's disease (AD). Based upon this approach, a series of novel 3,5-disubstituted isoxazoles and isothiazoles were prepared and evaluated in vitro as cholinergic channel activators (ChCAs) of neuronal nAChRs. Many of the 3-substituted 5-(2-pyrrolidinyl)isoxazoles were found to have nanomolar binding affinities comparable to (S)-nicotine (2a) in a preparation of whole rat brain. However, in a paradigm measuring the evoked release of [3H]dopamine from a preparation of rat striatum, there were differences in the agonist potencies and efficacies of these analogues relative to 2a. The differences in agonist potency observed between compounds of comparable binding potency may be due to differences in ligand interactions with various subtypes of neuronal nAChRs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|