Novel substituted 4-aminomethylpiperidines as potent and selective human beta3-agonists. Part 1: aryloxypropanolaminomethylpiperidines

Bioorg Med Chem Lett. 2002 Oct 21;12(20):2957-61. doi: 10.1016/s0960-894x(02)00607-8.

Abstract

The synthesis and SAR of a series of human beta3 adrenoreceptor agonists based on a template derived from a common pharmacophore coupled with 4-aminomethylpiperidine is described. Potent and selective agents were identified such as 26 that was in vitro active in CHO cells expressing human beta3-AR (EC50=49 nM, IA=1.1), and in vivo active in a transgenic mouse model.

MeSH terms

  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Humans
  • Indicators and Reagents
  • Mice
  • Mice, Transgenic
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology*
  • Receptors, Adrenergic, beta-3 / genetics
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Indicators and Reagents
  • Piperidines
  • Receptors, Adrenergic, beta-3