[Synthesis of dihydroindoline compounds and their anticholinesterase activity]

A series of dihydroindoline compounds were synthesized. The N-alkylation and O-acylation were controlled selectively by the presence or absence of phase transfer catalyst. The structure of compounds synthesized were ascertained by elemental analyses, 1HNMR, MS, and IR. The anticholinesterase activity was determined by modified Hestrin method and their pCI50 were calculated by Hill's pharmacodynamic formula. The structure-activity relationship was briefly discussed. (1) 5-carbamoyl group is the important factor for the anticholinesterase activity. If cyclic phosphoryl or sulfonyl group is used instead of the carbamoyl group, the inhibiting activity drops sharply. (2) Compounds in which C-3 of the indoline nucleus is quaternary are more potent than those in which C-3 is tertiary or secondary. So the methyl group at C-3 plays an important role in combining the inhibitor with the active center of cholinesterase by the hydrophobic bond. (3) When the indolines are changed into 2-indolinones the inhibiting activity drop steeply.