Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors

详细信息    查看全文

• 作者：Laurence Morellato^a ; Marie Lefas-Le Gall^a ; Michel Langlois^a ; Daniel-Henri Caignard^b ; Pierre Renard^b ; Philippe Delagrange^b ; Monique Mathé ; -Allainmat^c ; ^{monique.mathe@univ-nantes.fr}
• 关键词：Melatonin ; MT1 and MT2 receptors ; Bioisosteres ; Constrained ligands ; Agonism
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：23
• 期：2
• 页码：430-434
• 全文大小：529 K

文摘

N-(Arylcyclopropyl)acetamides and N-(arylvinyl)acetamides or methyl ureas have been prepared as constrained analogues of melatonin. The affinity of these new compounds for chicken brain melatonin receptors and recombinant human MT₁ and MT₂ receptors was evaluated using 2-[¹²⁵I]-iodomelatonin as radioligand. Strict ethylenic or cyclopropyl analogues of the commercialized agonist agomelatine (Valdoxan?) were equipotent to agomelatine in binding bioassays. However, the ethylenic analogue was more effective than the cyclopropyl one in the melanophore aggregation bioassay, but was still less potent than the disubstituted 2,7-dimethoxy-naphtalenic compounds.