Novel Imidazoline I2 Receptor Ligands for Alzheimer’s Disease

Imidazoline I2 receptors (I2-IRs) are widely distributed in the brain. I2-IRs are associated with analgesia and human brain disorders, such as depression and Alzheimer’s disease (AD). Since, a high density of I2-IRs proteins is observed in the brain of AD patients these receptors have been suggested as a potential therapeutic target for AD. The I2-IRs are still orphan proteins from a molecular point of view and the discovery of selective I2-IRs ligands is likely to enhance both, the AD therapeutic arsenal and serve as valuable tools in defining the pharmacological characterization of I2-IRs. From the structural point of view, I2-IRs ligands reported to date feature a 2-imidazoline substituted nucleus without decoration at any position, indicating that the nature of known IR ligands seems relatively restricted. We have recently reported the pharmacological characterization of a new family of (2-imidazoline-4-yl)phosphonates, prepared by a multicomponent microwaved-assisted reaction that fulfil the principl...