Synthesis, Anti-Inflammatory And Analgesic Activities Of Pyrrolepyrazinone And Pyrroleoxazinone Derivatives

The study on synthesis and structure-activity relationships (SAR) of (2H)-3,4-dihydropyrrolo[1,2-a]pyrazin-l-one C pyrrolepyrazinone ) and (1H)-3,4-dihydropyrrolo-[2,1-c][l,4]oxazin -l-one(pyrroleoxazinone) derivatives is reported in this paper.Based on the results of pyrrolizinone SAR, we designed and synthesized six 2-alkyl-pyrrolepyrazinones, forty-two 6-acyl-2-alkyl-pyrrolepyrazinones and twenty-eight 6-(phenyl-amino)methyl-2-alkyl-pyrrolepyrazinones as well as eight 6-acyl-pyrroleoxazinones and four 6-(phenylamino)methyl-pyrroleoxazinones in order to study on their SAR and develop new anti-inflammatory and analgesic agents with high efficacy and minimal side-effects.The anti-inflammatory and analgesic activities were tested in xylene-induced mice ear edema and acetic acid-induced mice writhing. Pharmacological studies showed that the synthesized compounds had potent anti-inflammatory and/or analgesic activities. Compounds ZF-05, 303, 353, 357, 359, 361, and 346 showed more potent anti-inflammatory than the control ibuprofen, and their analgesic activities were comparable to ibuprofen. They were regarded to be promising compounds to develop new anti-inflammatory and analgesic agents.Some SAR was discussed and 3D-QSAR of 6-acyl-2-alkyl-pyrrolepyrazinones has been studied by using CoMFA of CADD.