Structure-activity relationship studies of SEN12333 analogues: determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs.

Abstract Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described α7 agonist SEN12333 ( 8 ), have resulted in the identification of compound 45 , a potent and selective agonist of the α7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8 ).