Structural comparison between type I and type II antagonists: possible implications in the drug design of AT1 antagonists

Bioorg Med Chem Lett. 2000 Apr 17;10(8):755-8. doi: 10.1016/s0960-894x(00)00079-2.

Abstract

Analogues of sarilesin (type I AT1 antagonists), and sarmesin (type II AT1 antagonists) with homoserine (hSer) at position 8 were prepared and bioassayed. The presence of a Tyr4-Ile5-His6 bend found in sarmesin but not in sarilesin was identified. The obtained results coupled with conformational analysis studies, using a combination of NMR spectroscopy and computational chemistry, propose important conformational and stereoelectronic properties for agonist and antagonist activity at AT1 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / chemical synthesis
  • Angiotensin II / chemistry
  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Angiotensin Receptor Antagonists*
  • Animals
  • Drug Design
  • Female
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Rats
  • Receptors, Angiotensin / metabolism
  • Structure-Activity Relationship
  • Uterus / drug effects

Substances

  • Angiotensin Receptor Antagonists
  • Receptors, Angiotensin
  • Angiotensin II
  • angiotensin II, Sar(1)-Me-Tyr(4)-
  • Angiotensin I