Synthesis of selective COX2 inhibitors

Supervisor:

Dr. Murad Abualhasan

Abstract:

Classical NSAIDS inhibit both isoenzymes and has more side effects on gastric mucosa. While newer NSAIDS are more selective to COX-2 and are less irritant to gastric mucosa but have more cardiovascular events. Selectivity of COX-2 inhibitors is based on COX-2 enzyme structure which has a larger and more accessible binding site compared to COX1. In this study we designed a small library based on bulky diaryl and triaryl analogues with a polar moiety. The compounds were synthesized using Grignard reagent to make tertiary alcohols intermediates which was then coupled with the polar moiety using SN1 substitution reactions. The identification and some physicochemical properties of the synthesized compounds were determined using the available techniques in our research lab. The COX2 inhibition activity was performed using Cayman COX2 inhibition kit. The results showed variability in the COX2 inhibition activity among the synthesized compounds. Comp 7 showed a promising inhibition activity (46.3) and can be used as a lead compound for developing more active COX2 inhibitors.