[摘要]：The discovery of a series of small molecule alpha 4 beta 2 nAChR potentiators is reported. The structure-activity relationship leads to potent compounds selective against nAChRs including alpha 3 beta 2 and alpha 3 beta 4 and optimized for CNS penetrance. Compounds increased currents through recombinant alpha 4 beta 2 nAChRs, yet did not compete for binding with the orthosteric ligand cytisine. High potency and efficacy on the rat channel combined with good PK properties will allow testing of the a4b2 potentiator mechanism in animal models of disease. (C) 2008 Elsevier Ltd. All rights reserved.
