N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile relative to phenylpropanolamine and midodrine

J Med Chem. 2002 Sep 26;45(20):4395-7. doi: 10.1021/jm025550h.

Abstract

N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1) is a novel alpha(1) agent having the unique profile of alpha(1A) (rabbit urethra, EC(50) = 0.60 microM) agonism with alpha(1B) (rat spleen, pA(2) = 5.4) and alpha(1D) (rat aorta, pA(2) = 6.2) antagonism. An in vivo dog model showed 1 to be more selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the active metabolite of midodrine), and phenylpropanolamine (4).

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-Agonists / chemical synthesis*
  • Adrenergic alpha-Agonists / chemistry
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Adrenergic alpha-Antagonists / chemistry
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / physiology
  • Blood Pressure / drug effects
  • Dogs
  • Female
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Ligands
  • Midodrine / pharmacology*
  • Phenylpropanolamine / pharmacology*
  • Rabbits
  • Radioligand Assay
  • Rats
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Spleen / drug effects
  • Spleen / physiology
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology
  • Urethra / drug effects
  • Urethra / physiology

Substances

  • ABT 866
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Imidazoles
  • Ligands
  • Receptors, Adrenergic, alpha-1
  • Sulfonamides
  • Phenylpropanolamine
  • Midodrine