Design and synthesis of 3-phenyltetrahydronaphthalenic derivatives as new selective MT₂ melatoninergic ligands. Part II

详细信息    查看全文

• 作者：Sophie Durieux ; Angé ; line Chanu ; Christophe Bochu ; Valé ; rie Audinot ; Sophie Coumailleau ; Jean A. Boutin ; Philippe Delagrange ; Daniel H. Caignard ; Caroline Bennejean ; Pierre Renard ; Daniel Lesi
• 关键词：Melatonin ; Selective antagonists ; MT₂ receptors ; Tetralins
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：15 April 2009
• 年：2009
• 卷：17
• 期：8
• 页码：2963-2974
• 全文大小：380 K

文摘

Following our studies of the melatoninergic receptors, we have developed new tetrahydronaphthalenic derivatives of melatonin that have been tested as selective melatonin receptors ligands. Regarding the role of the phenyl substituent to obtain selective ligands, modulation of selectivity and activity have been achieved by modifications of the acyl group and substitutions on the phenyl ring. Ten of the seventeen evaluated derivatives have MT₂ receptor affinity similar to that of melatonin. Moreover, we have achieved remarkable MT₂ selectivity over MT₁ (selectivity >100) and have been able to further extend the RSA of the tetrahydrophthalenic series. However, the compounds presented here display partial agonist or antagonist behavior instead of full agonist.