Introduction

Current treatments for high cholesterol and cardiovascular diseases consist of healthy diet and/or administration of statins. With computer-based technologies and innovative synthesis we designed and produced novel molecules to inhibit PCSK9, a molecular target that differs from the target of the statin. The novel compounds might be more advantageous than commercial monoclonal antibodies.

Technical features

The conventional treatment for hypercholesterolemia and atherosclerosis is based on a low-fat diet and statin-based drugs. Unfortunately, a large fraction of patients responds only partially to the conventional treatment or has comorbidities that prevent the use of statins. Recently, some monoclonal antibodies (mAb), inhibiting a novel biological target known as PCSK9 and thus working differently from the statin mechanism, reached the pharmaceutical market. The use of monoclonal antibodies, however, is costly and implies an intramuscular injection every two weeks, penalising the patient’s compliance to the therapy. The invention here described consists of novel bi-heterocyclic PCSK9 inhibitors that are designed for oral administration and can be produced at lower costs. Such innovative small molecules, properly improved with computer-aided drug design techniques and with innovative organic synthesis, might be employed as cholesterol-lowering medications.

Possible Applications

• Hypercholesterolemia treatment;
• Myocardial infarction prevention;
• Atherosclerosis treatment;
• Treatment and prevention of cardiovascular diseases.

Advantages

• Oral administration is easier than intramuscular injection;
• Less expensive than commercially available medications acting on the same target;
• In case of side effects, the treatment might be immediately suspended, differently from an antibody-based therapy;
• Higher efficiency with respect to statins;
• Active on a different target with respect to statins.