4-tert-Pentylphenoxyalkyl derivatives - Histamine H3 receptor ligands and monoamine oxidase B inhibitors.
Bioorg Med Chem Lett
; 28(23-24): 3596-3600, 2018 12 15.
Article
em En
| MEDLINE
| ID: mdl-30404719
ABSTRACT
The synthesis and biological activity of 4-tert-pentylphenoxypropyl derivatives are described in this manuscript. All compounds (except one) showed human histamine H3 receptor affinity with Ki values below 760â¯nM. The inhibitory activity toward human monoamine oxidase B (hMAO B) was evaluated using a fluorometric Amplex-Red assay, and most of the compounds were effective in the submicromolar range. Among them, 1-(3-(4-tert-pPentylphenoxy)propyl)pyrrolidine (5) exhibited hMAO B inhibitory activity with an IC50 value of 4.5â¯nM. In addition, hMAO B inhibition by 5 was shown to be non-competitive and reversible. Further, recently described potent histamine H3 receptor ligands - 4-tert-pentylphenoxyalkyl derivatives (with a 4-8 carbon spacer) - were evaluated for hMAO B inhibitory activity, and some of them displayed activity in the submicromolar range. Selected compounds were also tested for human MAO A (hMAO A) inhibitory potencies and exhibited no activity. Moreover, molecular modeling studies were carried out for tested compounds to explain their molecular mechanism of hMAO B inhibition and the selectivity of compounds for hMAO B over hMAO A.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Receptores Histamínicos H3
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Ligantes
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Monoaminoxidase
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Inibidores da Monoaminoxidase
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Polônia