In order to improve the safety and mask the gastrointestinal (GI) side effects of the known anti-inflammatory drugs Ibuprofen, Diclofenac, Mefenamic acid, and Ketoprofen, each drug has been coupled to Propyphenzone (3  , 4  , 5  & 6  ) to form esterase-sensitive mutual prodrug. The structures of the newly synthesized adducts were confirmed by different spectroscopic techniques (1HNMR and MS). Their analgesic and anti-inflammatory activities as well as their selectivity towards COX I and COX II enzymes were investigated. The results revealed that the newly synthesized propyphenazone adducts were able to exert in-vivo anti-inflammatory and analgesic activities with improved potency than the use of each drug individually. The in-vitro ability of each prodrug to inhibit COXI and/or COXII has been switched on upon incubation with bovine esterase suggesting the ability of plasma esterase to process these prodrugs. Interestingly, coupling of Propyphenazone to 4-Aminoantipyrine (8  ), to form a non-prodrug adduct, showed remarkably improved anti-inflammatory activity in-vivo and unique COXII selectivity in-vitro. The in-vitro COXII inhibitory activity of this adduct (8)  was not affect by incubation was bovine esterase.

Structure modifications of some non-steroidal anti-inflammatory drugs improved their safety and altered their selectivity

247th National Meeting (2014)

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