Pierce J B, Ariyan Z S, Ovenden G S
J Med Chem. 1982 Feb;25(2):131-6. doi: 10.1021/jm00344a008.
Several N-alkyl- and N-arylacetoacetamides have been self-condensed to form pyridones. N-Alkylacetoacetamides give 2-pyridones, while N-arylacetoacetamides give 4-pyridones. In an attempt to develop nonacidic, nonsteroidal antiinflammatory agents, the pyridones were tested in a carrageenan-induced pedal edema assay in rats. While the 2-pyridones were not active, 9 of 17 4-pyridones tested were active, and one compound (4g) had antiinflammatory efficacy in a dose-response assay (ED50 values). Most compounds were considered nontoxic by determination of approximate LD50 values in mice by a standard multidimensional observational assay.
几种N-烷基和N-芳基乙酰乙酰胺已进行自身缩合反应以形成吡啶酮。N-烷基乙酰乙酰胺生成2-吡啶酮，而N-芳基乙酰乙酰胺生成4-吡啶酮。为了开发非酸性、非甾体类抗炎药，在大鼠角叉菜胶诱导的足跖水肿试验中对吡啶酮进行了测试。虽然2-吡啶酮没有活性，但所测试的17种4-吡啶酮中有9种具有活性，并且一种化合物（4g）在剂量反应试验（ED50值）中具有抗炎功效。通过标准的多维度观察试验测定小鼠的近似半数致死量值，大多数化合物被认为是无毒的。
