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
- Publication date
- Publisher
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 <b>1b</b> (GAT107) and (−)-enantiomer <b>1a</b> did
not affect its activity when coapplied. X-ray crystallography studies
revealed the absolute stereochemistry of <b>1b</b> to be 3a<i>R</i>,4<i>S</i>,9b<i>S</i>. <b>1b</b> represents the most potent ago-PAM of α7 nAChRs available
to date and is considered for further in vivo evaluation