Synthesis and pharmacological evaluation of novel arylpiperazine oxicams derivatives as potent analgesics without ulcerogenicity

[Display omitted] •New arylpiperazine oxicams derivatives were designed and synthesized.•Compounds obtained proved to be between two and five times analgesically more potent than the reference drug piroxicam.•New derivatives did not show any ulcerogenic activity. Gastrotoxicity continues to be a major issue in therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Medicine is yet to develop absolutely safe analgesics. Numerous strategies are employed to discover new, safer NSAIDs, for example selective inhibition of cyclooxygenase-2, new molecular targets (e.g. microsomal prostaglandin E2 synthase-1), incorporation of cytoprotective compounds in the drug molecule or modification of the classic NSAIDs currently available on the market. The research presented in this paper is indicative of a current worldwide trend in this area of science, and is an example of the fourth strategy noted above. Two series of new arylpiperazine derivatives of the classic NSAID – piroxicam, were developed by conventional synthesis. The full range of compounds obtained proved to be between two and five times analgesically more potent than the reference drug and, most importantly, they did not show any ulcerogenic activity.