Intramolecular Friedel-Crafts reaction of indoles with carbonyl groups: A simple synthesis of 3- and 4-substituted β-carbolin-1-ones
The intramolecular Friedel-Crafts reaction of indole-2-carboxylic acid β-oxoamides catalyzed by trifluoroacetic acid or InCl3, is a convenient method for the synthesis of 3-aryl-, 4-aryl-, and 4-alkyl-β-carbolin-1-ones. Georg Thieme Verlag Stuttgart.
Cincinelli, Raffaella,Dallavalle, Sabrina,Merlini, Lucio
experimental part
p. 1309 - 1312
(2009/04/06)
Synthesis, modeling, and RET protein kinase inhibitory activity of 3- and 4-substituted β-carbolin-1-ones
A series of β-carbolin-2-ones and 3,10-dihydro-2H-azepino[3,4-b]indol- 1-ones have been designed, synthesized, and evaluated as RET protein kinase inhibitors on the basis of their structural similarity with the prototype indolin-2-one RPI-1. Some β-carbolin-2-ones (structure 2) showed an ability to inhibit RET enzymatic activity in vitro and proliferation of RETC634R oncogene-transformed NIH3T3 cells comparable to that of the reference compound. The docking analysis of the interaction of these compounds with the crystallographic structure of RET tyrosine kinase domain suggested a new binding interaction scheme different from the one proposed during their design. The rigid structure of the compounds of this series represents a new scaffold with potential advantages in the design of RET protein kinase inhibitors.