Novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: a patent review

Abstract

Introduction: Cardiovascular disease (CVD) is a leading cause of death worldwide and hypercholesterolemia, or elevated low-density lipoprotein cholesterol (LDL-C), is a key risk factor. The standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of coronary heart disease and secondary prevention of coronary events.

Areas covered: This review summarizes the patent literature and advances in the discovery and development of new HMG-CoA reductase inhibitors from 2000 to 2010.

Expert opinion: The discovery of statins has had significant impact on reducing the worldwide burden of cardiovascular disease; nevertheless, the fact that heart disease remains a leading cause of death indicates that additional efforts are still needed. Using current statins, most patients at low and moderate risk of CVD reach recommended LDL-C targets, but a significant portion of patients in the high risk category fail to achieve optimal LDL-C targets. The potential introduction of novel statins with increased efficacy and tolerability profiles may represent an opportunity to further reduce the incidence of cardiovascular disease. Herein, I review the patent literature and examine the properties of several next generation statin clinical candidates.