Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation

Amino Acids. 2011 Feb;40(2):411-20. doi: 10.1007/s00726-010-0651-y. Epub 2010 Jul 6.

Abstract

A series of o-, m- and p-benzyl tetrazole derivatives 11a-c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / chemical synthesis*
  • Angiotensin Receptor Antagonists / chemistry
  • Angiotensin Receptor Antagonists / pharmacology*
  • Animals
  • Cell Line
  • Drug Design*
  • Humans
  • Kinetics
  • Male
  • Models, Molecular
  • Protein Binding
  • Rabbits
  • Rats
  • Receptors, Angiotensin / chemistry
  • Receptors, Angiotensin / metabolism
  • Structure-Activity Relationship
  • Urocanic Acid / chemistry*

Substances

  • Angiotensin Receptor Antagonists
  • Receptors, Angiotensin
  • Urocanic Acid