Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1

Bioorg Med Chem Lett. 2004 Jan 5;14(1):177-80. doi: 10.1016/j.bmcl.2003.09.066.

Abstract

Inhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Biological Availability
  • Cation Transport Proteins / antagonists & inhibitors*
  • Cation Transport Proteins / metabolism
  • Cell Line
  • Guanidines / administration & dosage*
  • Guanidines / chemistry
  • Guanidines / pharmacokinetics
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / chemistry
  • Imidazoles / pharmacokinetics
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors*
  • Sodium-Hydrogen Exchangers / metabolism
  • Stereoisomerism

Substances

  • Cation Transport Proteins
  • Guanidines
  • Imidazoles
  • Membrane Proteins
  • Protein Isoforms
  • SLC9A1 protein, human
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers