Synthesis of diversely substituted pyridin-2(1 H )-ones and in vivo evaluation of their anti-allodynic effect on cutaneous inflammatory mechanical allodynia.

A series of 3,5-disubtituted pyridin-2(1 H )-ones was synthesized. As part of a structure-activity relationship study performed in this series, structural modifications were based on 3-(indol-4-yl)-5-(pyridin-4-ylamino)pyridin-2(1 H )-one B, which exhibited a potent anti-allodynic effect in a rat model of inflammatory pain. In this study, new compounds were assessed for their ability to inhibit cutaneous mechanical allodynia in rats by using the capsaicin pain model. Compound 36, a 2-methoxypyridine derivative, yielded the most promising outcome, demonstrating an enhanced analgesic effect.