Design, synthesis, computational and biological evaluation of new anxiolytics.

New anxiolytics have been discovered by prediction of biological activity with computer programs pass and derek for a heterogeneous set of 5494 highly chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a-fused imidazoles and others). The majority of tested compounds exhibit the predicted anxiolytic effect. The most potent activity was found in 2-(4-nitrophenyl)-3-(4-phenylpiperazinomethyl)imidazo[1,2-a]pyridine 8, 1-[(4-bromophenyl)-2-oxoethyl]-3-(1,3-dioxolano)-2-indolinone 3, 5-hydroxy-3-methoxycarbonyl-1-phenylpyrazole 5 and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-a]pyridine 7. The application of the computer-assisted approach significantly reduced the number of synthesized and tested compounds and increased the chance of finding new chemical entities (NCEs).