Advertisement

Substrate Analogue Renin Inhibitors Containing Replacements of Histidine in P2 or Isosteres of the Amide Bond Between P3 and P2 Sites

  • P. Raddatz
  • A. Jonczyk
  • C. J. Schmitges
  • J. Sombroek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)

Abstract

The search for orally active renin inhibitors as therapeutic agents continues to represent a challenging target for medicinal chemists.1 Analogues of the angiotensinogen region flanking the bond split by renin have turned out to be very potent and specific inhibitors of renin. However, the high affinity of these angiotensinogen analogues for human renin is often associated with fast hydrolysis between P3 and P2 sites by the intestinal serine protease chymotrypsin.2

Keywords

Renin Inhibitor Human Renin Fast Hydrolysis Porcine Pepsin Challenging Target 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. J. Greenlee, Med. Res. Rev. 10: 173 (1990); W. J. Greenlee, Pharm. Res. 4:364 (1987); J. M. Wood, J. L. Stanton and K. G. Hofbauer, J. Enzyme Inhibition 1:169 (1987); H. D. Kleinen, Am. J. Hypertens. 2:800 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    Nomenclature as described by I. Schechter and A. Berger, Biochem. Biophys. Res. Comm. 27: 157 (1967).PubMedCrossRefGoogle Scholar
  3. 3.
    M. J. Humphrey and P. S. Ringrose, Drug Metab. Rev. 17: 283 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Boger, L. S. Payne, D. S. Perlow, M. Poe, E. H. Blaine, E. H. Ulm, T. W. Schorn, B. LaMont, M. G. Bock, R. M. Freidinger, B. E. Evans and D. F. Veber, Ninth American Peptide Symposium, Toronto, (1985).Google Scholar
  5. 5.
    M. Szelke, D. H. Jones, A. Hallett and B. Atrash, WO 84/03044.Google Scholar
  6. 6.
    P. Raddatz, H. E. Radunz, G. Schneider and H. Schwarz, Angew. Chem. 100: 414 (1988); For a review see: H.-J. Altenbach, Nachr. Chem. Tech. Lab. 36:756 (1988).CrossRefGoogle Scholar
  7. 7.
    For a review see: R. Herming, Nachr. Chem. Tech. Lab. 38: 460 (1990).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • P. Raddatz
    • 1
  • A. Jonczyk
    • 1
  • C. J. Schmitges
    • 1
  • J. Sombroek
    • 1
  1. 1.E. MerckPharrnaforschungDarmstadtGermany

Personalised recommendations