Aromatic ring functionalization of benzolactam derivatives: New potent dopamine D3 receptor ligands

Since the discovery of the dopamine D3 receptor, an intensive effort has been directed toward the development of potent and selective ligands in order to elucidate the function and potential therapeutic advantages of targeting D3 receptors. As a part of our efforts, a novel series of substituted benzolactams derivatives was synthesized mostly through palladium-catalyzed reactions. Their affinities on D1–D4 receptors were evaluated and the data led us to highly potent D3 ligands, some of them highly selective for D3 receptor, compared to the related dopamine receptor subtypes. Functional D3 activity assays of the most relevant compounds have been carried out revealing antagonist as well as partial agonist activity.

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