Design, synthesis, computational and biological evaluation of new anxiolytics
Athina A. Geronikaki, Eugene V. Babaev, John C. Dearden, Wim Dehaen, Dmitry A. Filimonov, Irina Galaeva, Valentina Krajneva, Alexey A. Lagunin, Fliur Macaev, Г. М. Молодавкин, Vladimir Poroikov, Serghei I. Pogrebnoi, В. И. Салоутин, Alla V. Stepanchikova, Eugenia Stingaci, Natalia Tkach, Liudmila Vlad, Татьяна Александровна Воронина · Bioorganic & Medicinal Chemistry · 2004
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).