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Antihypertensives: Renin Inhibitors

Cardiovascular, Endocrine and Metabolic Diseases

  1. Colin M. Tice,
  2. Gerard M. McGeehan,
  3. David A. Claremon

Published Online: 15 SEP 2010

DOI: 10.1002/0471266949.bmc181

Burger's Medicinal Chemistry and Drug Discovery

Burger's Medicinal Chemistry and Drug Discovery

How to Cite

Tice, C. M., McGeehan, G. M. and Claremon, D. A. 2010. Antihypertensives: Renin Inhibitors. Burger's Medicinal Chemistry and Drug Discovery. 239–266.

Author Information

  1. Vitae Pharmaceuticals, Fort Washington, PA

Publication History

  1. Published Online: 15 SEP 2010


Renin has been recognized as an attractive target for antihypertensive drugs since the 1950s. Intensive efforts in the 1980s focused on peptidomimetic hydroxy transition-state isosteres led to many potent renin inhibitors. However, none of these compounds was developed as a drug. The advent of routine X-ray crystallography of protein–ligand complexes provided additional insights that culminated in the discovery of aliskiren, a fully nonpeptidic renin inhibitor. Aliskiren, the first direct renin inhibitor to reach the market, was approved as an antihypertensive in 2007. Preliminary clinical trials suggest that aliskiren, and potentially other direct renin inhibitors, may have utility in end organ protection and congestive heart failure, in addition to hypertension.


  • aspartyl proteases;
  • hypertension;
  • renin;
  • X-ray crystallography