Introduction

The present invention refers to isoindoline derivatives able to activate AMPK (AMP-activated protein kinase), a protein complex playing a crucial role as a master regulator of cellular energy homeostasis. The novel compounds can be used in both the prophylaxis and the treatment of metabolic disorders, such as type II diabetes and obesity, but also immune-mediated inflammatory pathologies and cancer.

Technical features

AMPK plays a key role as a master regulator of cellular energy homeostasis, being activated in response to stresses that deplete cellular ATP supplies. Moreover, it critically contributes to the modulation of immune/inflammatory cell functions and is also involved in stemming carcinogenesis, counteracting most of the metabolic changes occurring in rapidly proliferating cells by acting on their metabolic status. Therefore, it represents a viable therapeutic target for the treatment of metabolic disorders but also immune-mediated inflammatory pathologies and cancer.
The novel isoindoline derivatives described in the patent have been designed to directly interact with AMPK, triggering its activation.
In vitro tests showed a significant increase in AMPK phosphorylation, at a concentration of 10 μM, proving more potent stimulatory effect than that displayed by the commercially available AMPK activator Berberine (BBR), tested at the same concentration.

Possible Applications

• Prophylaxis and treatment of immune-mediated inflammatory disorders;
• Prophylaxis and treatment of type II diabetes;
• Prophylaxis and treatment of obesity;
• Prophylaxis and treatment of tumours.

Advantages

• Original synthetic compounds endowed with chemical stability and water solubility;
• Chemical entities obtained from simple reactants through efficient, economic and sustainable synthetic procedures;
• Good bioavailability and tolerability.