ACETYLCHOLINE-RELEASE ENHANCERS RELATED TO LINOPIRDINE - A STRUCTURE-ACTIVITY RELATIONSHIP STUDY .2.

Several series of alpha,alpha-disubstituted polycyclic compounds were found to enhance the stimulus-induced release of neurotransmitters, es pecially acetylcholine, in brain slices. This work resulted in the ide ntification of linopirdine idinylmethyl)-1,3-dihydro-1-phenyl-2H-indol -2-one] 1a which was tested clinically for the treatment of Alzheimer' s disease. The structure-activity relationship (SAR) results suggest t hat the potency of the series was dependent on the nature of the pende nt groups (R), the distance geometry produced by the pendant groups, a nd the hydrogen-bonding property of the core group.