||Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used medicines for the treatment of pain and inflammation today. They perform this function by way of inhibition of prostaglandin synthase, or COX. Prostaglandin synthase is the enzyme responsible for the production of prostaglandins, bioactive molecules that trigger the inflammation response in the body. NSAIDs are categorized into two basic varieties: time dependent (tight binding), and time independent (reversible competitive). Time independent NSAIDs bind in the active site of prostaglandin synthase by the same mechanism as the enzyme's natural substrate, arachidonic acid. As a result, time independent NSAIDs exhibit classical competitive inhibition. Once a time dependent NSAID finds its way into the active site, it becomes lodged in there for an extended period of time. For this reason, time dependent NSAIDs are more effective analgesics and anti-inflammatory drugs. The synthesis of time-dependent NSAIDs is also central to the development of isoform selective NSAIDs, a very prominent area of medicinal chemistry. Flurbiprofen, a known time dependent NSAID, differs in structure from ibuprofen, a known time independent NSAID, in two ways. It has a fluorine atom that ibuprofen lacks, and it has a phenyl group where ibuprofen has a sec-butyl group. Previous research has shown that time dependence is not determined by the presence of the fluorine group. For this project, a series of six analogues of ibuprofen were synthesized and assayed using a visible absorbance kinetic assay. Different alkyl groups were substituted for the sec-butyl group with the goal of determining the structural requirements of the 5 alkyl group necessary for time dependent inhibition. Of the six analogues tested, only three were inhibitors of prostaglandin synthase: one with a cyclohexyl group, one with a cyclopentyl group, and one with a cycloheptyl group. All three of these NSAIDs were determined to be time independent, with the cyclohexyl analogue being the most potent. The lack of time-dependence displayed by these cycloalkyl NSAIDs suggests that the aromaticity of flurbiprofen's phenyl group is of key importance to its tight-binding behavior. This finding is in support of previous crystallographic studies of COX-1 crystallized in the presence of flurbiprofen, which suggested that a phenyl-hydroxyl hydrogen bond had formed between the phenyl group of flurbiprofen and the hydroxyl hydrogen on Ser-530 in the active site of COX-1. Future studies will attempt to synthesize heterocyclic rings to add a hydrogen bond acceptor to the NSAID alkyl substituent to see if this confers time dependence to NSAID inhibition.