Introduction

The present invention refers to benzofuran derivatives able to activate AMPK (Adenosine MonoPhosphate-activated protein Kinase), a key enzyme for the regulation of immune homeostasis. These compounds represent effective drug candidates for the prevention and treatment of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis.

Technical features

Inflammatory Bowel Diseases (IBDs) are chronic immune-mediated disorders of the digestive tract, characterized by intestinal inflammation and epithelial injury and having a major impact on individuals quality of life. It is well known that the protein complex AMPK exerts a beneficial effects on gut health, suppressing its inflammatory condition and enhancing its barrier function. Therefore, activation of this key protein represents a viable strategy for the treatment of this kind of disorders.
The novel benzofuran derivatives described in the patent have been designed to trigger AMPK activation, thus representing valuable drug candidates for the treatment of IBDs. Besides activating the target protein in vitro, these compounds display a relevant anti-inflammatory efficacy when tested in a mouse model of acute colitis, proving to ameliorate both systemic- and tissue-related inflammatory parameters. All inflammatory parameters examined were improved by treatment: body and spleen weight, colon length, macroscopic damage at the epithelial level and Tnfalpha and MDA levels.

Possible Applications

• Prophylaxis and theapy of inflammatory bowel diseases;
• Prophylaxis and therapy of Crohn’s disease;
• Prophylaxis and therapy of ulcerative colitis;
• Prophylaxis and therapy of immune-mediated inflammatory disorders.

Advantages

• Original synthetic compounds endowed with chemical stability and water solubility;
• Obtained from simple reactants through efficient, economic and sustainable synthetic procedures;
• Endowed with good bioavailability and tolerability.