Durieux Sophie, Chanu Angéline, Bochu Christophe, Audinot Valérie, Coumailleau Sophie, Boutin Jean A, Delagrange Philippe, Caignard Daniel H, Bennejean Caroline, Renard Pierre, Lesieur Daniel, Berthelot Pascal, Yous Saïd
Laboratoire de Chimie Thérapeutique (EA 1043), Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France.
Bioorg Med Chem. 2009 Apr 15;17(8):2963-74. doi: 10.1016/j.bmc.2009.03.023. Epub 2009 Mar 18.
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 MT(2) receptor affinity similar to that of melatonin. Moreover, we have achieved remarkable MT(2) selectivity over MT(1) (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.
在对褪黑素能受体进行研究之后，我们开发了新型的褪黑素四氢萘衍生物，并将其作为选择性褪黑素受体配体进行了测试。关于苯基取代基在获得选择性配体中的作用，通过对酰基的修饰和苯环上的取代实现了选择性和活性的调节。所评估的17种衍生物中有10种对MT(2)受体的亲和力与褪黑素相似。此外，我们实现了对MT(2)相对于MT(1)的显著选择性（选择性>100），并且能够进一步扩展四氢萘系列的受体亚型选择性活性（RSA）。然而，此处展示的化合物表现出部分激动剂或拮抗剂行为，而非完全激动剂行为。
