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

Ibrahim Alkabodi, Sadik Almekh

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