Novel Triazolopyrimidinone Compounds as Inhibitors of Adipocyte Fatty Acid-Binding Protein (FABP4)

Metabolic syndrome, characterized by a combination of high blood pressure, elevated blood glucose levels, high triglycerides, low HDL cholesterol, and abdominal obesity, significantly increases the risk of coronary heart disease, diabetes, and stroke. Fatty acid-binding proteins (FABPs), particularly FABP4, play a crucial role in these processes, serving as lipid chaperones that regulate lipid responses in adipocytes and macrophages. Recent advances in FABP4 inhibitor (FABP4i) development have shown potential in improving insulin resistance and related metabolic conditions in experimental models. The design of new FABP4i compounds, particularly those based on the [1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one core structure, offers promising strategies for treating obesity-related metabolic disorders. In this study, a group of triazolopyrimidine-7-on derivatives was synthesized, and their FABP4i activity was evaluated. Compound 1 was found to be the most active, with one-third of the activity of arachidonic acid.