二氢吲哚类化合物的合成及其抑酶活性

本文报道了一系列二氢吲哚衍生物的合成,并测定其抑制胆碱酯酶活性,发现二氢吲哚环被二氢吲哚酮结构所取代,3位季碳被仲碳原子所取代,5位以可能有抑制酶活性的环磷酰基或磺酰基代替二甲氨甲酰基,均使抑酶活性几乎完全消失。在合成过程中,使1位N-烃化或5位O-酰化选择性地进行。

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 pCl_(50) 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.