Introduction

The present invention relates to the design, the new synthesis and the biological evaluation of novel bicyclic compounds with a secretagogue activity of GLP-1 hormone. These derivatives represent an important tool for the treatment of type 2 diabetes, obesity and non-alcoholic fat leaver disease (NAFLD), as they could substitute the expensive treatments now in use worldwide.

Technical features

The invention is related to the completely new chemistry developed to access novel sp³ rich 1,3-diazo-4-oxa-[3.3.1]-bicyclo nonene scaffolds. The new stable compounds showed to be active at the micromolar range on GLP-1 secretion. This is a fundamental point as the stimulation of GLP-1 hormone may be considered a very important target in pharmaceutical field. In fact, their activity can be conveniently exploited for the introduction in therapy of new orally active drugs for the treatment of type 2 diabetes, obesity and non-alcoholic fat leaver disease (NAFLD).
Most GLP-1 agonists already available for the treatment of type 2 diabetes and obesity, such as exenatide and liraglutide, are peptides and therefore need a parenteral administration. The new small organic molecules can be, instead, orally active, affording benefits in the therapy management.

Possible Applications

• Treatment of type 2 diabetis;
• Treatment of obesity;
• Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD);
• Preventive effect of degenerative diseases (Alzheimer, Parkinson).

Advantages

• The molecules are chemically original;
• The new molecules are stable;
• Possibility in oral administration;
• Improved patient compliance regarding the therapy in use;
• Low therapeutic costs.