Dual Target Ligands with 4-tert-Butylphenoxy Scaffold as Histamine H3 Receptor Antagonists and Monoamine Oxidase B Inhibitors.

ABSTRACT: Dual target ligands are a promising concept for the treatment of Parkinson's disease (PD). A combination of monoamine oxidase B (MAO B) inhibition with histamine H3 receptor (H3R) antagonism could have positive effects on dopamine regulation. Thus, a series of twenty-seven 4-tert-butylphenoxyalkoxyamines were designed as potential dual-target ligands for PD based on the structure of 1-(3-(4-tert-butylphenoxy)propyl)piperidine (DL76). Probed modifications included the introduction of different cyclic amines and elongation of the alkyl chain. Synthesized compounds were investigated for human H3R (hH3R) affinity and human MAO B (hMAO B) inhibitory activity. Most compounds showed good hH3R affinities with Ki values below 400 nM, and some of them showed potent inhibitory activity for hMAO B wit

SUBMITTER: Lazewska D 

PROVIDER: S-EPMC7279487 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature