Synthesis, Biological Evaluation, and Docking Studies of Antagonistic Hydroxylated Arecaidine Esters Targeting mAChRs.

ABSTRACT: The muscarinic acetylcholine receptor family is a highly sought-after target in drug and molecular imaging discovery efforts aimed at neurological disorders. Hampered by the structural similarity of the five subtypes' orthosteric binding pockets, these efforts largely failed to deliver subtype-selective ligands. Building on our recent successes with arecaidine-derived ligands targeting M₁, herein we report the synthesis of a related series of 11 hydroxylated arecaidine esters. Their physicochemical property profiles, expressed in terms of their computationally calculated CNS MPO scores and HPLC-logD values, point towards blood-brain barrier permeability. By means of a competitive radioligand binding assay, the binding affinity values towards each of the individual human mAChR su

SUBMITTER: Kilian J 

PROVIDER: S-EPMC9145622 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature