Non-steroidal anti-inflammatory medicines are routinely given medications that have a variation of side-effects, including gastrointestinal ulcers as well as cardiovascular problems. We evaluated the direct cyclooxygenase (COX) inhibitory activity and studied the probable COX binding manner of certain previously described 2-(trimethoxyphenyl)-thiazoles in order to find safer NSAIDs. COX inhibition experiments were carried out in-vitro using ovine COX-1 & human recombinant COX-2. To understand the putative interactions between the inhibitors and the binding pockets of both COX isoforms, molecular docking experiments were conducted. Inflammation is a complex process that is required for human defence mechanisms but also has a role in the progression of various sicknesses. The finding of cyclooxygenase-2 (COX2) enhanced the pharmacology of non-steroidal anti-inflammatory medications (NSAIDs), offering a pure mechanism for prostaglandin control in-vivo and a novel target for COX-2-selective therapies with no GI side effects. Some literature papers must highlighted the effect of these anti-inflammatory agents in treatments, highlighting the importance of this pharmacological class. Until 2016, the most recent published literature on COX-2 inhibitors was considered in this paper. The most current advancements in this medicinal family are described using a broad chemical classification, emphasizing structure-activity correlations insights & mechanisms. There is also a summary of the most common side effects as well as an outline of the novel prospective healing indications for COX-2 inhibitors.