Novel effective small-molecule inhibitors of protein kinases related to tau pathology in Alzheimer's disease.
Future Med Chem
; 14(16): 1175-1186, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35920260
Background: Alzheimer's disease (AD) drugs in therapy are limited to acetylcholine esterase inhibitors and memantine. Newly developed drugs against a single target structure have an insufficient effect on symptomatic AD patients. Results: Novel aromatically anellated pyridofuranes have been evaluated for inhibition of AD-relevant protein kinases cdk1, cdk2, gsk-3b and Fyn. Best activities have been found for naphthopyridofuranes with a hydroxyl function as part of the 5-substituent and a hydrogen or halogen substituent in the 8-position. Best results in nanomolar ranges were found for benzopyridofuranes with a 6-hydroxy and a 3-alkoxy substitution or an exclusive 6-alkoxy substituent. Conclusion: First lead compounds were identified inhibiting two to three kinases in nanomolar ranges to be qualified as an innovative approach for AD multitargeting.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido