Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1523-6. doi: 10.1016/j.bmcl.2012.01.013. Epub 2012 Jan 14.

Abstract

We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both β(2)-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC(50)=0.278 μM, which was more potent than phthalazinone, IC(50)=0.520 μM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50)=9.3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists* / chemistry
  • Adrenergic beta-2 Receptor Agonists* / pharmacology
  • Animals
  • Asthma / drug therapy*
  • Drug Design*
  • Guinea Pigs
  • Inhibitory Concentration 50
  • Molecular Structure
  • Phosphodiesterase 4 Inhibitors / chemistry*
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Trachea / drug effects*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Phosphodiesterase 4 Inhibitors