Studies On Biological Activities Molecule With Piperidine Ring

No matter natural or synthetic piperidine derivatives exhibit an extensive range of biological activities such as anti-tumor, anti-inflammatory, anxiolytics, anti-epileptics. Piperidine is a normal constituent in mammalian brain, affects synaptic mechanism in the CNS. Nipecotic acid display in vitro as inhibitors of [3H]-GABA transporters. GABA transporters are important therapeutical targets in epilepsy and potentially other neurological diseases related to the GABA system. The selective inhibitors of GABA transporters can enhance GABA concentration of synapse so as to be a major enhancement of GABA ergic neurotransmission function. It is hopeful to develop relevant treatment medicine of disease relative to GABA ergic neurotransmission such as anti-epileptics, anti-convulsion, and analgesics.It was found that the piperidine derivatives possessed potent inhibitory activity of GAT-1 but seldom found the publications in China. In order to further study on the selective inhibitors of GABA transports, GAT-1 was regarded as biological targets in our research. Tiagabine and NNC-711 were selected to be lead compounds so as to design and synthesize a series of synthetic piperidine derivatives and study their biological activities. On the other hand, a series of organic sulfur compounds were designed and synthesized by sulfur atom in the chain instead of a methylene group of Tiagabine, and sulfur ether compounds further oxidized. The inhibited activities of GABA transporters of these new organic sulfur compounds were tested in vitro. Reticuline is a natured isoquinoline alkaloid with many important biological activities, especially biological activity in CNS. Reticuline can be regarded as a lead compound to design and synthesize a series of natural piperidine derivatives. The [3H]-GABA uptake inhibition bioassays of all synthetic compounds were done in Institute of Shanghai Institutes of Cell biology & Biochemistry.During our studies, 166 compounds, including 53 target compounds, were synthesized. Among the 166 compounds, 112 are new compounds.