Design, synthesis, computational and biological evaluation of new anxiolytics

Abstract New anxiolytics have been discovered by prediction of biological activity with computer programs PASS and DE 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 nitro phenyl) 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)

SYNTHESIS OF PINONIC ACID NEW DERIVATIVES

The method for synthetising new derivatives of the pinonic acid using, at the key step, the reaction of condensation with epichlorohydrin, has been elaborated. It has been shown that, in the presence of catalytic amount of tetrabutylammonium chloride, the reaction is directed towards the formation of etherchlorohydrin, which, later on, is easily transformed into epoxides as well as chloromethyldiketones with good overall yield