Development of novel ß2-adrenergic receptor agonists for the stimulation of glucose uptake - The importance of chirality and ring size of cyclic amines.
Bioorg Med Chem Lett
; 97: 129562, 2024 01 01.
Article
em En
| MEDLINE
| ID: mdl-37967654
ABSTRACT
ß2-Adrenergic receptor (ß2AR) agonists have been reported to stimulate glucose uptake (GU) by skeletal muscle cells and are therefore highly interesting as a possible treatment for type 2 diabetes (T2D). The chirality of compounds often has a great impact on the activity of ß2AR agonists, although this has thus far not been investigated for GU. Here we report the GU for a selection of synthesized acyclic and cyclic ß-hydroxy-3-fluorophenethylamines. For the N-butyl and the N-(2-pentyl) compounds, the (R) and (R,R) (3d and 7e) stereoisomers induced the highest GU. When the compounds contained a saturated nitrogen containing 4- to 7-membered heterocycle, the (R,R,R) enantiomer of the azetidine (8a) and the pyrrolidine (9a) had the highest activity. Altogether, these results provide pivotal information for designing novel ß2AR agonist for the treatment of T2D.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Agonistas de Receptores Adrenérgicos beta 2
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article