Molecular hybridization yields triazole bronchodilators for the treatment of COPD

Abstract A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β 2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of ‘inhalation by design’ furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties.