Abstract
Dual-target-directed agents simultaneously inhibiting glycogen phosphorylase (GP) and activating glucokinase (GK) could decelerate the inflow of glucose from glycogenolysis and accelerate the outflow of glucose in the liver, therefore allow for a better control over hyperglycaemia in a synergetic manner. A series of hybrid compounds were designed by structure-assisted and ligand-based strategies. In vitro bioassays found two novel compounds (1j, 6g) worthy of further optimization on balance of dual action to GP and GK. In addition, for single-target activity, two compounds exhibited more potent GP inhibitory activity and four compounds showed better GK activation than their corresponding references.
Original language | English (US) |
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Pages (from-to) | 624-639 |
Number of pages | 16 |
Journal | European Journal of Medicinal Chemistry |
Volume | 58 |
DOIs | |
State | Published - Dec 2012 |
Externally published | Yes |
Keywords
- Dual-target-directed
- Glucokinase activators
- Glycogen phosphorylase inhibitors
- Hybrid
- Type 2 diabetes
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry