SYNTHESIS AND ANTI-INFLAMMATORY ANALGESIC ACTIVITIES OF PHENYLFUROXAN-COUPLED DICLOFENAC

AIMTo search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects. METHODSCoupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo. RESULTSFifteen new compounds including nine target ones (II_1～9) were synthesized, and their structures were determined by IR, ¹HNMR, MS and elemental analysis. Compounds II₃ and II₉ showed anti-inflammatory activity comparable to DC. Compound II₂ showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo. CONCLUSIONCompound II₂ is worthy to be intensively studied.