Synthesis & Structure-Activity Relationship Studies of Phenyltetrazole Derivatives as P2X3 Receptor Antagonists

Abstract

Neuropathic pain is caused by lesion or disease in the nervous system. P2X3 receptors are expressed selectively in Aδ and C fibers in primary afferent neurons and are involved in neuropathic pain. In the previous screening, β-amino alcohol phenyltetrazole benzyl compound was selected as hit compound of P2X3 receptor antagonist. Thus, phenyltetrazole derivatives were synthesized as P2X3 receptor antagonist. To see the effect of alkyl group and carbon chain length, various alkyl group was introduced or removed and carbon chain length was regulated. And, to confirm the need of amine group and hydroxyl group, various derivatives were synthesized. P2X3 receptor antagonist activity was confirmed by calcium influx assay using the P2X3 receptor or P2X2/3 receptor expressing cell line. Through the assay results, structure–activity relationship study was progressed based on structure of phenyltetrazole derivatives. Therefore, this study suggests possibility of the phenyltetrazole derivatives as P2X3 receptor antagonist for neuropathic pain treatment.