Synthesis and receptor docking studies of N-substituted indole-2-carboxylic acid esters as a search for COX-2 selective enzyme inhibitors

A series of N-substituted indole-2-carboxylic acid esters have been prepare d by replacing the benzoyl group of indomethacin with a benzyl and a phenyl group. The carbocyclic acid side chain was extended via creating an ester structure by using several dialkylaminoalkyl groups. The receptor docking s tudies were performed to investigate the docking mode of each compound by u sing DOCK 4.0. All the compounds were shown to be docked at the site where intact flurbiprofen was embedded for COX-1 and s-58 (1-phenylsulphonamide-3 -trifluoromethyl-5-para-bromophenylpyrazole) for COX-2. It was predicted th at N-phenyl-indole-2-carboxylic acid piperazine ester 22 can be a fairly st rong COX-2 selective compound which was compared to the others. Other predi cted COX-2 selective compounds included are N-H indole-2-carboxylic acid di ethyl 30 and piperazine 34 esters. In view of these findings, compounds 22, 30 and 34 were chosen for the in vitro biological assays. (C) 2001 Edition s scientifiques et medicales Elsevier SAS.