Work

Norbenzomorphan Scaffold: Chemical Tool for Modulating Sigma Receptor-Subtype Selectivity

Year: 2017

Type: article

Abstract: 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.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.7b00066

Authors: James J. Sahn, Timothy R. Hodges, Jessica Z. Chan, Stephen F. Martin

Institution: The University of Texas at Austin

Language: English

Topic: Pharmacological Receptor Mechanisms and Effects

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green