An update on hybrid drugs in cardiovascular drug research

Abstract

Background: Several different strategies are commonly used in medicinal chemistry to develop new molecules targeted at improving the current pharmacotherapy of cardiovascular diseases and hypertension. Among these, in the past years, we could observe an increasing development of new hybrid compounds in which two or more mechanisms of action are combined together to give a new pharmacological entity targeting, simultaneously, several factors involved in complex cardiovascular diseases. Objective: The aim of this review is to present the rational pharmacological bases and the chemical approaches used for the development of representative hybrid drugs. Conclusions: In this paper, some promising multi-targeted enzyme inhibitors and dual receptor antagonists are reported. Some examples of pharmacodynamic hybrids compounds, in which a suitable nitric oxide releasing functionality has been added to known cardiovascular drugs, are also shown.

Keywords::

• cardiovascular pharmacotherapy
• endothelins
• hybrid drugs
• multi-target drugs
• neutral endopeptidase
• nitric oxide
• rennin–angiotensin system
• statins