Abstract

Homomeric α₇ nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation of cognitive processes such as memory and attention and have potential as therapeutic targets for the treatment of the cognitive deficits associated with schizophrenia. Though numerous α₇ nAChR agonists have been developed, and several have progressed to clinical trials, these are derived from few common chemotypes. Consequently, many of these α₇ nAChR clinical candidates share unfavorable side-effect profile. SEN12333 represents a novel chemotype for the development of α₇ nAChR agonists, and exploration of this scaffold has produced structurally diverse ligands with promising pharmacological properties. This review will summarize structure-affinity and -activity relationships surrounding analogs of SEN12333.

Keywords: Nicotinic receptors, schizophrenia, Alzheimer’s disease, SEN12333.