Positional isomers of bispyridine benzene derivatives induce efficacy changes on mGlu₅ negative allosteric modulation

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• 作者：Xavier Gó ; mez-Santacana^a ; ^b ; ^c ; ¹ ; James A.R. Dalton^b ; ^d ; Xavier Rovira^e ; ^f ; Jean Philippe Pin^e ; ^f ; Cyril Goudet^e ; ^f ; Pau Gorostiza^c ; ^g ; ^h ; Jesú ; s Giraldo^b ; ^d ; Amadeu Llebaria^a ; ^{amadeu.llebaria@iqac.csic.es}
• 关键词：mGlu5 ; Isomers ; Partial efficacy ; NAM ; Antagonist ; Inverse agonist
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：127
• 期：Complete
• 页码：567-576
• 全文大小：2176 K
• 卷排序：127

文摘

Efficacy of bispyridine benzene mGlu5 negative allosteric modulators depends on molecule geometry. 1,4-disubstituted linear compounds have mGlu5 partial antagonist activity. 1,3-disubstituted angular compounds have mGlu5 full inverse agonist activity. 1,4- and 1,3-isomers bind preferentially to different receptor conformations according to computational docking.