Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1354-8. doi: 10.1016/j.bmcl.2011.01.043. Epub 2011 Jan 18.

Abstract

We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptors.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / chemical synthesis*
  • Adrenergic beta-2 Receptor Agonists / chemistry
  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Bronchodilator Agents / chemical synthesis
  • Bronchodilator Agents / chemistry
  • Bronchodilator Agents / pharmacology
  • Drug Design*
  • Humans
  • Molecular Structure
  • Muscarinic Antagonists / chemical synthesis*
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / pharmacology*
  • Receptors, Adrenergic, beta-2* / chemistry
  • Receptors, Muscarinic* / chemistry
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Muscarinic Antagonists
  • Receptors, Adrenergic, beta-2
  • Receptors, Muscarinic