Expeditious Synthesis, Enantiomeric Resolution, and Enantiomer Functional Characterization of (4-(4-Bromophenyl)-3a,4,5,9b-tetrahydro-3<i>H</i>-cyclopenta[<i>c</i>]quinoline-8-sulfonamide (4BP-TQS): An Allosteric Agonist-Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors

Abstract

An expeditious microwave-assisted synthesis of 4BP-TQS, its enantiomeric separation, and their functional evaluation is reported. Electrophysiological characterization in Xenopus oocytes revealed that activity exclusively resided in the (+)-enantiomer 1b (GAT107) and (-)-enantiomer 1a did not affect its activity when coapplied. X-ray crystallography studies revealed the absolute stereochemistry of 1b to be 3aR,4S,9bS. 1b represents the most potent ago-PAM of α7 nAChRs available to date and is considered for further in vivo evaluation.