Cecilia Menciu, M. Duflos, Fabienne Fouchard
1999
Citations
0
Influential Citations
12
Citations
Journal
Journal of Medicinal Chemistry
Abstract
A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44−84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1−4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2-decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17−25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3-yl]acetamide 45, out of 41 compounds.This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 μM. Its inhibitory activity in IL-4 production...