Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine-Δ² -Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation.

ABSTRACT: Compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4H-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channel activation but can induce the α7 desensitized D_s state, which is sensitive to a type II positive allosteric modulator, such as PNU-120596. Introduction of meta substituents into the benzyloxy moiety of 11 led to two sets of tertiary amines and quaternary ammonium salts based on the spirocyclic quinuclidinyl-Δ² -isoxazoline scaffold. Electrophysiological assays performed on Xenopus laevis oocytes expressing human α7 nAChRs highlighted four compounds that

SUBMITTER: Quadri M 

PROVIDER: S-EPMC5573630 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature