Synthesis and in vitro characterization of N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8- tetrahydronaphthalen-1-yl]methanesulfonamide and its enantiomers: a novel selective alpha 1A receptor agonist

J Med Chem. 1996 Sep 27;39(20):4116-9. doi: 10.1021/jm960354u.

Abstract

The existence of multiple subtypes of the alpha 1 adrenergic receptor has been demonstrated both pharmacologically and by molecular biological cloning techniques. The development of subtype selective antagonists has been the focus of much research within the pharmaceutical industry, and clinical evidence now exists that alpha-1A selective antagonists will have utility in the treatment of benign prostatic hyperplasia. However, highly subtype selective agonists are not known. Herein we report the synthesis and pharmacological characterization of N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8- tetrahydronaphthalen-1-yl]methanesulfonamide and its enantiomers, a highly potent full agonist with excellent selectivity for the alpha 1A receptor subtype.

MeSH terms

  • Adrenergic alpha-Agonists / chemical synthesis*
  • Adrenergic alpha-Agonists / metabolism
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Cattle
  • Cricetinae
  • Dogs
  • Imidazoles / chemical synthesis*
  • Imidazoles / metabolism
  • Imidazoles / pharmacology
  • Male
  • Rats
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / metabolism
  • Tetrahydronaphthalenes / pharmacology

Substances

  • A 61603
  • Adrenergic alpha-Agonists
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • Tetrahydronaphthalenes