Issue 2, 2018

Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors

Abstract

A series of (−)-nornuciferidine derivatives was synthesized and the non-natural enantiomer of the aporphine alkaloid was discovered to be a potent β1- and β2-adrenergic receptor ligand that antagonized isoproterenol and procaterol induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic analogues revealed that the conformationally restricted (6a-R,7-R)-7-hydroxyaporphine 2 (AK-2-202) was necessary for efficient receptor binding and antagonism.

Graphical abstract: Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors

Supplementary files

Article information

Article type
Research Article
Submitted
31 Dec 2017
Accepted
05 Jan 2018
First published
22 Jan 2018

Med. Chem. Commun., 2018,9, 353-356

Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors

A. F. Ku and G. D. Cuny, Med. Chem. Commun., 2018, 9, 353 DOI: 10.1039/C7MD00656J

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