Design And Synthesis Of New Neuropathic Pain Treatment Drugs

Neuropathic pain is arising as a direct consequence of a lesion or disease affecting the somatosensory system.It is defined as a chronic pain state,which can devastate spontaneous pain,hyperalgesia,allodynia and paresthesia.The pathogenesis of neuropathic pain is not very clear now,and it is lack of a satisfied way to treat it.A novel approach to pain therapy is to disrupt the PSD95-nNOS interaction of the NMDAR-PSD95-nNOS signalling pathway.It allows specific inhibition of the NMDAR-nNOS signaling pathway,without affecting the physiological function of the NMDAR and nNOS,thus reducing the release of NO.It is a good way to reduce apoptosis and injury of neuronal.Inhibitors of the PSD95-nNOS protein-protein which is synthesized by our lab can only demonstrate action by intravenous injection or intrathecal injection because of its low Blood Brain Barrier.So,it brings much inconvenience for our experiment.The mechanism of action and the SAR(structure-activity relationship)of ZL006 have been studied through preliminary research.As to the hydrophobic side,-Cl/-Br are substituted.As to the hydrophilic side,-COOH is modified to-COOR(R=C10H17)and-CONHR(R=C9H15O2).Through this modification above,it is hope to improve activity of these compounds by changing the lipo-hydro partition coefficient.17 target compounds have been designed and synthesized.The pharmacological experiment result shows that 8 compounds have analgesic effect in neuropathic pain,which provides a direction for future research and reference.