Discovery of novel 1,2,4-triazol-5-ones as tumor necrosis factor-alpha inhibitors for the treatment of neuropathic pain.

In this work, synthetic integration of substituted semicarbazides and various aliphatic, aryl and heteroaryl acids into 1,2,4-triazol-5-ones was accomplished. Following the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluated in two peripheral models of neuropathic pain, the chronic constriction injury and partial sciatic nerve ligation to assess their antihyperalgesic and antiallodynic potential. ED(50) studies undertaken for selected compounds exhibiting promising efficacies (1c, 3c and 4a) revealed values ranging from 13.