Discovery and characterization of novel TRPML1 agonists.
Bioorg Med Chem Lett
; 98: 129595, 2024 Jan 15.
Article
de En
| MEDLINE
| ID: mdl-38141860
ABSTRACT
Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tétrazoles
/
Canaux cationiques TRP
Langue:
En
Journal:
Bioorg Med Chem Lett
/
Bioorg. med. chem. lett
/
Bioorganic & medicinal chemistry letters
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2024
Type de document:
Article
Pays de publication:
Royaume-Uni