Synthesis of New 2,3-Dihydroindole Derivatives and Evaluation of Their Melatonin Receptor Binding Affinity

Abstract

2,3-Dihydroindoles are promising agents for the synthesis of new compounds with neuroprotective and antioxidant properties. Usually, these compounds are obtained by direct reduction of the corresponding indoles containing acceptor groups in the indole ring for its activation. In this work, we propose a synthetic strategy to obtain new 2,3-dihydroindole derivatives from the corresponding polyfunctional 2-oxindoles. Three methods were proposed for reduction of functional groups in the 2-oxindole and 2-chloroindole molecules using various boron hydrides. The possibility of chemoselective reduction of the nitrile group in the presence of an amide was shown. The proposed synthetic strategy can be used, for example, for the synthesis of new analogs of the endogenous hormone melatonin and other compounds with neuroprotective properties.

Editorial: Biofunctional Molecule Exploratory Research on Application in Food and Health

“…Meanwhile, the 2,3-Dihydroindoles represent a group of promising agents that exhibit neuroprotective and antioxidant properties. Herein, Volkova et al have reported the synthesis of new 2,3-dihydroindole derivatives as potential melatonin receptor ligands [ 5 ]. The research team used several boron hydrides to reduce the functional groups within 2-oxindole and 2-chloroindole molecules, and they proposed that a NaBH 4 /NiCl 2 reagent led to cyano-group reduction while BH 3 -based reagents produced simultaneous reductions in both cyano- and amido-groups of the oxindole ring.…”

Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity

“…Recently, considerable attention has been paid to melatonin and dopamine receptors as promising targets in the search for antiglaucoma drugs [ 17 , 18 ], which causes interest in oxindole derivatives as well. Previously, we have observed that 2-oxindole derivatives can reduce IOP in animal models and have antioxidant properties [ 19 , 20 , 21 , 22 , 23 ]. The most promising were recognized as 3-hydroxy-2-oxindoles.…”