A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated invivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50=0.18, 0.24, 0.28 and 0.36μM; respectively) and selectivity index (SI) range of 363-668. Invitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50=0.18μM), and an extremely selective [COX-2 (SI)=668] comparable to celecoxib [COX-2 (SI)>384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50=54.0mg/kg) relative to diclofenac (ED50=114mg/kg).Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02Å), Arg(513) (1.94, 2.83Å), and Gln(192) (3.25Å).