Acetylcholine release enhancers related to linopirdine: A structure-activity relationship study. II

Article abstract of DOI:10.1016/0223-5234(96)80369-2

Several series of α,α-disubstituted polycyclic compounds were found to enhance the stimulus-induced release of neurotransmitters, especially acetylcholine, in brain slices. This work resulted in the identification of linopirdine [3,3-bis(4-pyridinylmethyl)-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 that the potency of the series was dependent on the nature of the pendent groups (R), the distance geometry produced by the pendant groups, and the hydrogen-bonding property of the core group.