Hybrids consisting of the pharmacophores of salmeterol and roflumilast or phthalazinone: dual β₂-adrenoceptor agonists-PDE4 inhibitors for the treatment of COPD

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1548-52. doi: 10.1016/j.bmcl.2012.11.058. Epub 2012 Nov 29.

Abstract

A novel class of dual pharmacology bronchodilators targeting both β(2)-adrenoceptor and PDE4 was designed and synthesised by combining the pharmacophores of salmeterol and roflumilast or phthalazinone. All the compounds exhibited better β(2)-adrenoceptor agonist activities (pEC(50)=8.47-9.20) than the reference compound salmeterol (pEC(50)=8.3) and good inhibitory activity on PDE4B2 (IC(50)=0.235-1.093 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / chemistry
  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Albuterol / analogs & derivatives*
  • Albuterol / chemistry
  • Albuterol / pharmacology
  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacology*
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Bronchodilator Agents / pharmacology
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Humans
  • Phosphodiesterase 4 Inhibitors / chemistry
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Salmeterol Xinafoate

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Aminopyridines
  • Benzamides
  • Bronchodilator Agents
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast
  • Salmeterol Xinafoate
  • Albuterol