Modern methods of drug design rely not only on developing a compound that exhibits a good pharmacological parameters but also should be easy to synthesize. This approach will significantly reduce the possible production costs of the future drug [1]. Ipsapiron is a partial agonist to the 5-HT1A receptor [2], belonging to the group of long-chain arylpiperazines (LCAPs) and having antidepressant and anti-anxiety properties [2]. Recent work of our team allowed to simplify the synthetic path and shorten the synthesis time of Ipsapiron from dozen hours to 2 minutes. Now it was decided to study the structure-activity relationship (SAR) by modifying the length of the alkyl chain and the aryl ring at the piperazine moiety. The new compounds were obtained in solvent-free reactions supported by a microwave irradiation. This method can be considered as fast, efficient and consistent with the trends of green chemistry. In the first step, the bromoalkyl / aryl saccharin was synthesized, and then obtained intermediate was alkylated with the corresponding arylpiperazines. The reaction time usually did not exceed 5 minutes. The final product was purified by crystallization or by chromatographic methods. A new compounds, were designed using molecular modelling and computational methods (Cresset and Schroodinger software packages). The calculated physicochemical parameters determining the properties of drug-like compounds were also considered. Each of the ligands obtained was tested in in vitro assay for the binding to the D2 and 5-HT1A receptor. Preliminary results of biological tests for saccharin derivatives with a hexyl chain show that the compounds have very good affinity to the D2 and 5-HT1A receptor.

Synthesis and biological activity of a new saccharine derivatives as a dual D2/5-HT1A receptor ligands

2019 Spring National Meeting

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