Dibenzofuranylethylamines as 5-HT_2A/2C Receptor Agonists.

ABSTRACT: The human 5-HT₂ receptor subtypes have high sequence identity in their orthosteric ligand-binding domain, and many agonists are poorly selective between the 5-HT_2A and 5-HT_2C subtypes. Nevertheless, their activation is associated with different pharmacological outcomes. We synthesized five phenethylamine analogs in which the benzene ring is replaced by a bulky dibenzo[b,d]furan moiety and found a couple with >70-fold 5-HT_2C selectivity. Molecular docking studies of the most potent compound (5) at both receptor subtypes revealed the likely structural basis of its selectivity. Although in both cases, some crucial interactions are conserved, the change of the Ala222^5.46 residue in the 5-HT_2C receptor to the

SUBMITTER: Yempala T 

PROVIDER: S-EPMC7016908 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature