Norbenzomorphan Scaffold: Chemical Tool for Modulating Sigma Receptor-Subtype Selectivity
| Autor: | Timothy R. Hodges, Stephen F. Martin, James J. Sahn, Jessica Z. Chan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Sigma-1 receptor 010405 organic chemistry Stereochemistry Chemistry fungi Organic Chemistry Sigma receptor Sigma Sigma-2 receptor Ring (chemistry) 01 natural sciences Biochemistry Small molecule 0104 chemical sciences 03 medical and health sciences 030104 developmental biology Drug Discovery Pharmacophore Binding site |
| Zdroj: | ACS Medicinal Chemistry Letters. 8:455-460 |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.7b00066 |
| Popis: | Some norbenzomorphans exhibit high affinity for sigma 1 and sigma 2 receptors, and varying the position of substituents on the aromatic ring of this scaffold has a significant effect on subtype selectivity. In particular, compounds bearing several different substituents at C7 of the norbenzomorphan ring system exhibit a general preference for the sigma 1 receptor, whereas the corresponding C8-substituted analogues preferentially bind at the sigma 2 receptor. These findings suggest that the norbenzomorphan scaffold may be a unique chemical template that can be easily tuned to prepare small molecules for use as tool compounds to study the specific biological effects arising from preferential binding at either sigma receptor subtype. In the absence of structural characterization data for the sigma 2 receptor, such compounds will be useful toward refining the pharmacophore model of its binding site. |
| Databáze: | OpenAIRE |
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