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

Lyn H Jones; Helen Baldock; Mark E Bunnage; Jane Burrows; Nick Clarke; Michele Coghlan; David Entwistle; David Fairman; Neil Feeder; Craig Fulton; Laura Hilton; Kim James; Rhys M Jones; Amy S Kenyon; Stuart Marshall; Sandra D Newman; Rachel Osborne; Sheena Patel; Matthew D Selby; Emilio F Stuart; Michael A Trevethick; Karen N Wright; David A Price

doi:10.1016/j.bmcl.2010.10.132

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

Bioorg Med Chem Lett. 2011 May 1;21(9):2759-63. doi: 10.1016/j.bmcl.2010.10.132. Epub 2010 Oct 31.

Affiliation

¹ Sandwich Chemistry, World Wide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK. lyn.jones@pfizer.com

PMID: 21075627
DOI: 10.1016/j.bmcl.2010.10.132

Abstract

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.

MeSH terms

Administration, Inhalation
Adrenergic beta-2 Receptor Agonists* / administration & dosage
Animals
Benzhydryl Compounds / administration & dosage
Cresols / administration & dosage
Drug Design*
Drug Therapy, Combination
Guinea Pigs
Molecular Structure
Muscarinic Antagonists* / administration & dosage
Phenylpropanolamine / administration & dosage
Pulmonary Disease, Chronic Obstructive / drug therapy*
Tolterodine Tartrate

Substances

Adrenergic beta-2 Receptor Agonists
Benzhydryl Compounds
Cresols
Muscarinic Antagonists
Phenylpropanolamine
Tolterodine Tartrate