From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists

Bioorg Med Chem Lett. 2012 Jan 1;22(1):689-95. doi: 10.1016/j.bmcl.2011.10.049. Epub 2011 Oct 20.

Abstract

Libraries of dibasic compounds designed around the molecular scaffold of the DA(2)/β(2) dual agonist sibenadet (Viozan™) have yielded a number of promising starting points that have been further optimised into novel potent and selective target molecules with required pharmacokinetic properties. From a shortlist, 31 was discovered as a novel, high potency, and highly efficacious β(2)-agonist with high selectivity and a duration of action commensurable with once daily dosing.

MeSH terms

  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Asthma / drug therapy
  • Bronchodilator Agents / pharmacology
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods*
  • Cyclic AMP / metabolism
  • Drug Design
  • Guinea Pigs
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Protein Binding
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Thiazoles / pharmacology
  • Time Factors

Substances

  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Thiazoles
  • Cyclic AMP
  • sibenadet