Analogs of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 2. The amide bond "B-region"

A series of analogues of capsaicin, the pungent principle of chilli peppers, was synthesised and tested in assays for capsaicin-like agonism in vitro. The results of these assays with activities in an acute nociceptive model and a correlation was observed which established that the results of these in vitro assays were predictive of analgesia. Using a modular approach the structureactivity profile of specific regions of capsaicin congeners was established using an in vitro assay measuring 45 Ca 2+ uptake into neonatal rat dorsal root ganglia neurones. Substituted benzylnonanamides 2a-z and N-octyl-substituted phenylacemides 4a-v were made to test the requirements for activity in the aromatic «A-region» of the molecule