Abstract
Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.
Original language | English (US) |
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Pages (from-to) | 366-373 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 22 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2014 |
Externally published | Yes |
Keywords
- AKT inhibitors
- GSK3β
- Inhibition rate
- Tetra-substituted indoles
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry