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Published on: April 6, 2017
Molecular hybridization yields triazole bronchodilators for the treatment of COPD
Lyn H Jones1, Jane Burrows2, Neil Feeder2
1WorldWide Medicinal Chemistry, 610 Main Street, Cambridge, MA 02139, USA.
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 β2 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.
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