Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) whose actions are mediated by inhibition of cyclooxygenase-2 (COX-2, IC50 < 1 �M).  Diclofenac has also been shown in vitro to inhibit the sustained current of acid-sensing ion channel 3 (ASIC-3), a sodium-conducting ion channel that is thought to be involved in pain signaling, when the channel is activated by acidification to pH 4 (IC50 = 92 �M). Because inhibition of ASIC-3 may represent a new approach to pain pharmacotherapy, we synthesized diclofenac analogues in which modifications were made to the acetic acid group in an attempt to identify a strong ASIC-3 inhibitor with low activity toward COX-2.  The synthesis of the diclofenac analogues will be described as well as the results of their use in inhibition assays against COX-2 and ASIC-3.

Inhibition of COX-2 and ASIC-3 by structural analogs of diclofenac

243rd National Meeting (2012)

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