Aromatic ring functionalization of benzolactam derivatives: New potent dopamine D-3 receptor ligands

作者：Ortega Raquel^*; Huebner Harald; Gmeiner Peter; Masaguer Christian F

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(9): 2670-2674.

DOI：10.1016/j.bmcl.2010.12.083

• Dopamine receptors
• Antipsychotics
• Structure-activity relationship
• Benzolactams
• Arylpiperazines

Since the discovery of the dopamine D-3 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 D-3 receptors. As a part of our efforts, a novel series of substituted benzolactams derivatives was synthesized mostly through palladium-catalyzed reactions. Their affinities on D-1-D-4 receptors were evaluated and the data led us to highly potent D-3 ligands, some of them highly selective for D-3 receptor, compared to the related dopamine receptor subtypes. Functional D-3 activity assays of the most relevant compounds have been carried out revealing antagonist as well as partial agonist activity.

• 出版日期2011-5-1