Synthesis of New Acetaminophen Analogs and Their Ibuprofen Conjugates as Novel Analgesic Drugs

Abstract

In this research, new analogs of acetaminophen (paracetamol, I) with dimethyl and ethyl substitutions on phenyl moiety and sulfonamide modified by inserting alkylpiperazine derivatives were synthesized (II – V). Then, their conjugated compounds with ibuprofen were also synthesized (VI – IX) and the analgesic and anti-inflammatory activities of new drugs (II – IX) were evaluated in formalin tests on rats. Results indicated that the best analgesic activity was observed for compounds II and VI in diminishing chronic and VI – IX in acute thermal pain tests; in addition, compound VIII showed the best activity in diminishing inflammation. It was concluded that chemical structural binding of the potent synthesized drugs (II – V) with ibuprofen produced new superior antinociceptive and anti-inflammatory drugs (VI – IX) which could alleviate both pain and inflammation.