Multitarget Cardiovascular Drugs

U.      Trstenjak; D.      Kikelj

Abstract

Cardiovascular disease is the number one cause of death globally. Design of cardiovascular drugs based on new paradigms is therefore a prominent goal of medicinal chemistry. Designed multiple ligands, targeting two or more proteins involved in pathogenesis of disease have become a viable concept in drug discovery. Although adjustment of the activities ratio at the different targets is a demanding and challenging task, modulation of two or more targets involved in a cardiovascular disease may be more successful for therapeutic application than treatment directed against each target alone, because of improved pharmacodynamic and pharmacokinetic properties of designed multitarget drugs. The article reviews the applications of multitarget approach to cardiovascular drug design, covering angiotensin-converting enzyme/neutral endopeptidase inhibitors, neutrale endopeptidase/endothelin-converting enzyme inhibitors, angiotensin-converting enzyme/neutral endopeptidase/endothelin-converting enzyme inhibitors, dual angiotensin/endothelin receptor and angiotensin1/angotensin2 receptor antagonists and angiotensin receptor antagonist/neutral endopeptidase inhibitors.

Keywords: Angiotensin-converting enzyme, neutral endopeptidase, endothelin-converting enzyme, angiotensin receptor, endothelin receptor, multitarget drugs, pathogenesis, medicinal chemistry, cardiovascular