Benzothiophene derivatives as phosphodiesterase 10A (PDE10A) inhibitors: Hit-to-lead studies.
Bioorg Med Chem Lett
; 29(11): 1419-1422, 2019 06 01.
Article
en En
| MEDLINE
| ID: mdl-30952590
ABSTRACT
A novel series of benzothiophene derivatives was discovered as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity relationship studies on high-throughput screening hit compound 1 led to the identification of 7-acetyl-3-methyl-N-(quinolin-2-yl)-1-benzothiophene-2-carboxamide (16), with potent inhibitory activity (PDE10A IC50â¯=â¯7.6â¯nM) and selectivity (>1300-fold selectivity over the other tested phosphodiesterases). In addition, a novel methyl-induced conformational alteration of the benzothiophene-2-carboxamide derivatives is reported.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Tiofenos
/
Hidrolasas Diéster Fosfóricas
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article