Preparation and antiplasmodial activity of 3',4'‐dihydro‐1' H ‐spiro(indoline‐3,2'‐quinolin)‐2‐ones

A series of 3',4'‐dihydro‐1' H ‐spiro(indoline‐3,2'‐quinolin)‐2‐ones were prepared by the inverse‐electron‐demand aza‐Diels–Alder reaction (Povarov reaction) of imines derived from isatin and substituted anilines, and the electron‐rich alkenes trans‐ isoeugenol and 3,4‐dihydro‐2 H ‐pyran. These compounds were assessed for in vitro antiplasmodial activity against drug‐sensitive and drug‐resistant forms of the P. falciparum parasite. Three compounds derived from 3,4‐dihydro‐2 H ‐pyran and four compounds derived from trans‐ isoeugenol showed antiplasmodial activity in the low micromolar range against the drug‐resistant FCR‐3 strain (1.52–4.20 µM). Only compounds derived from trans‐ isoeugenol showed antiplasmodial activity against the drug‐sensitive 3D7 strain (1.31–1.80 µM).