Synthesis and anti-inflammatory activity of novel aspirin and ibuprofen amide derivatives

Abstract

This study includes design and synthesis of new non-steroidal anti-inflammatory agents (NSAIDs) to achieve better activity and low gastric side effects. Two series of compounds have been designed and synthesized as potential NSAIDs, these are: aspirin derivatives (compounds 1, 2) and ibuprofen derivatives (compounds 3&4). The major side effects associated with all currently available NSAIDS are gastrointestinal tract (GIT) hemorrhage and ulceration, due to inhibition of COX-1, which is responsible for biosynthesis of cyto-protective prostaglandins E2, while COX-2 is synthesized in response to proinflammatory stimuli such as, cytokines. Structural modification of available traditional NSAIDS, might be improve their specificity for COX-2 enzyme selectivity. These derivatives were prepared from Aspirin and Ibuprofen that conjugated with 2-Amino-5 - ethyl �1, 3, 4-thiadiazole, and 2- Amino-5- trifluoromethyl -1, 3, 4-thiadiazole respectively using N, N-dicyclohexylcarbodiimide (DCC) as coupling agent. The structures of synthesized compounds were confirmed by IR spectra and 1H NMR spectra . The preliminary pharmacological evaluation indicate that compounds 1 N-[5- ethyl -1,3,4-thiadiazole ]- phenyl acetate showed maximal anti-inflammatory activity with less ulcero-genic effect, while compound 3 (2-(4-Isobutyl phenyl) - N-[5-ethyl-2-(1,3,4- thiadiazolyl)]-propamide) showed least ulcer indexes these effects may be refer to the presence of certain structural features of heterocyclic ring