Design, synthesis and evaluation of novel hydroxyethylamine derivatives with nitrogen heterocyclic moiety at N-terminal as BACE1 inhibitors
- Author:
Kan ZHAO
1
Author Information
1. Institute of Pharmacology and Toxicology
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
BACE1;
Hydroxyethylamine;
Inhibitor
- From:
Journal of International Pharmaceutical Research
2010;37(5):377-381
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To develop a new series of hydroxy ethylamine (HEA) BACE1 inhibitors with nitrogen heterocyclic moiety at N-terminal and find new N-terminal moiety for enhancing BACE1 inhibition activity. Methods: New HEA compounds with nitrogen heterocyclic moiety at N-terminal were synthesized and evaluated as BACE1 inhibitors,with (-)-epigallocatechin-3-gallate EGCG as a positive control. Results: All new compounds were characterized by 1H NMR and ESI-MS. Evaluation of BACE1 inhibition activity showed that the compound I6 with indole moiety at N-terminal had BACE1 inhibition activity. Conclusion: The results suggested that the indole moiety at N-terminal interact with S2 pocket of BACE1 and be favorable for enhancing BACE1 inhibition activity, Thus, the indole moiety at N-terminal can be used as lead structure for further finding more effient BACE1 inhibitors.
