Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4612-6. doi: 10.1016/j.bmcl.2011.05.097. Epub 2011 Jun 13.

Abstract

Starting with the molecular scaffold of the DA(2)/β(2) dual agonist sibenadet (Viozan™), a number of molecular changes were incorporated, which were designed to increase the potency and selectivity of the target molecule, and improve its pharmacokinetics. Through this process a novel, high potency, full β(2)-agonist with high selectivity and long duration capable of being dosed once daily has been discovered.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / chemical synthesis
  • Adrenergic beta-2 Receptor Agonists / chemistry*
  • Adrenergic beta-2 Receptor Agonists / pharmacokinetics
  • Animals
  • Bronchodilator Agents / chemical synthesis
  • Bronchodilator Agents / chemistry*
  • Bronchodilator Agents / pharmacokinetics
  • Drug Design
  • Drug Evaluation, Preclinical
  • Guinea Pigs
  • Receptors, Adrenergic, beta-2 / chemistry*
  • Receptors, Adrenergic, beta-2 / metabolism
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacokinetics

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Receptors, Adrenergic, beta-2
  • Thiazoles
  • sibenadet