Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates

In this paper, we report the design, synthesis and pharmacological evaluation of a series of pyrazine N-acylhydrazone (NAH) derivatives (2a-s), planned by molecular simplification of prototype LASSBio-1018 (1). The series (2a-s) was evaluated in several animal models of pain and inflammation. All compounds presented important antinociceptive and anti-inflammatory profiles, especially compound 2o (LASSBio-1181), presenting a trimethoxylated phenyl moiety. This derivative 2o has shown better pharmacological profile than prototype 1, being also active in adjuvant-induced arthritis test in rats.