Inhalation by design: Dual pharmacology β-2 agonists/M3 antagonists for the treatment of COPD

• Published in: Bioorganic & medicinal chemistry letters 2011-05, Vol.21 (9), p.2759-2763
• Main Authors: Jones, Lyn H., Baldock, Helen, Bunnage, Mark E., Burrows, Jane, Clarke, Nick, Coghlan, Michele, Entwistle, David, Fairman, David, Feeder, Neil, Fulton, Craig, Hilton, Laura, James, Kim, Jones, Rhys M., Kenyon, Amy S., Marshall, Stuart, Newman, Sandra D., Osborne, Rachel, Patel, Sheena, Selby, Matthew D., Stuart, Emilio F., Trevethick, Michael A., Wright, Karen N., Price, David A.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Animals; antagonists; Benzhydryl Compounds - administration & dosage; Biological and medical sciences; breathing; Catecholaminergic system; chemistry; Cholinergic system; COPD; Cresols - administration & dosage; Crystallinity; Drug Design; Drug Therapy, Combination; Dual pharmacology; Guinea Pigs; Inhalation; MABA; Medical sciences; Molecular Structure; Muscarinic Antagonists - administration & dosage; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; pharmacokinetics; Pharmacology. Drug treatments; Phenylpropanolamine - administration & dosage; Pulmonary Disease, Chronic Obstructive - drug therapy; Respiratory system; Tolterodine Tartrate
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.10.132

This paper describes the successful design and development of dual pharmacology β-2 agonists-M3 antagonists, for the treatment of chronic obstructive pulmonary disorder using the principles of ‘inhalation by design’. A key feature of this work is the combination of balanced potency and pharmacodynamic duration with desirable pharmacokinetic and material properties, whilst keeping synthetic complexity to a minimum.