SAR of α7 nicotinic receptor agonists derived from tilorone: Exploration of a novel nicotinic pharmacophore
| Autor: | Jennifer M. Frost, Jianguo Ji, William H. Bunnelle, Tao Li, Murali Gopalakrishnan, David J. Anderson, Kevin B. Sippy, Carol S. Surowy, Michael Meyer, Clark A. Briggs, Michael R. Schrimpf |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Agonist
alpha7 Nicotinic Acetylcholine Receptor medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Tilorone Plasma protein binding Receptors Nicotinic Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Structure–activity relationship Nicotinic Agonists Receptor Molecular Biology Fluorenes Molecular Structure Organic Chemistry Rats Nicotinic agonist Fluorenone chemistry Molecular Medicine Pharmacophore Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:1633-1638 |
| ISSN: | 0960-894X |
| Popis: | The well-known interferon-inducer tilorone was found to possess potent affinity for the agonist site of the α7 neuronal nicotinic receptor (K(i)=56 nM). SAR investigations determined that both basic sidechains are essential for potent activity, however active monosubstituted derivatives can also be prepared if the flexible sidechains are replaced with conformationally rigidified cyclic amines. Analogs in which the fluorenone core is replaced with either dibenzothiophene-5,5-dioxide or xanthenone also retain potent activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect