Tetrahydroisoquinoline derivatives containing a benzenesulfonamide moiety as potent, selective human beta3 adrenergic receptor agonists

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2283-6. doi: 10.1016/s0960-894x(00)00459-5.

Abstract

Tetrahydroisoquinoline derivatives containing a 4-(hexylureido)benzenesulfonamide were examined as human beta3 adrenergic receptor (AR) agonists. Notably, 4,4-biphenyl derivative 9 was a 6 nM full agonist of the beta3 AR. Naphthyloxy compound 18 (beta3 EC50 = 78 nM) did not activate the beta1 and beta2 ARs at 10 microM, and showed >1000-fold selectivity over binding to the beta1 and beta2 ARs.

MeSH terms

  • Adrenergic beta-3 Receptor Antagonists*
  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / pharmacology
  • Amides / chemical synthesis*
  • Amides / chemistry
  • Drug Design
  • Humans
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-3 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Amides
  • Isoquinolines
  • Peptides
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • Recombinant Proteins