Historical overview, development and new approaches in the design of angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Part I.

Abstract

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of hypertension, congestive heart failure, and chronic renal failure. In addition to a discussion of the current understanding of the chemical structures and the modes of action of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor (ATR) antagonists, this review includes their SAR analysis and a chemical modification for improving their activity. Nowadays, different modeling strategies are underway to develop tailor-made molecules with the best of properties among nonpeptide renin inhibitors, dual action receptor antagonists (e.g. angiotensin and endothelin antagonists, ACE/NEP inhibitors, AT1/TxA2 antagonists, balanced AT1/AT2 antagonists), triple inhibitors. In the first part an overview of various ACE inhibitors is given. The second part is devoted to an overview of angiotensin receptor antagonists. The advances that have been made, new opportunities, and future directions of design and development of these classes are discussed.