Progress in the Development of Inhaled Long Acting P2Adrenoceptor Agonists

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Paul A. Glossop and David A. Price

Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich,

Kent, CT13 9NJ, UK

Long acting ^-adrenoceptor agonists are a highly precedented drug class used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) [1,2]. There are currently two marketed long acting ^-adrenoceptor agonists, salmeterol 1 [3], and formoterol 2 [4,5], neither of which provides a once daily dosing regimen. Therefore, an opportunity may exist for a once daily agent both as a mono-therapy and as part of combination products, particularly with steroidal or muscarinic ligands. This review is not intended to cover the current state of potential combination therapies; however, the final section of this review deals with an alternative paradigm of incorporating a second pharmacology within the same molecule as |b2-adrenoceptor agonism. This concept is referred to as dual pharmacology [6].

Asthma is a chronic inflammatory disorder of the airways causing recurrent episodes of wheezing, breathlessness, chest tightness, and coughing [7]. These symptoms often occur at night or in the early morning, impacting sleep patterns and so reducing overall quality of life. COPD is the fourth leading cause of death in the US and is characterized by airflow obstruction due to chronic bronchitis or emphysema

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOLUME 41 © 2006 Elsevier Inc.

ISSN: 0065-7743 DOI 10.1016/S0065-7743(06)41015-0 All rights reserved

Contents

1. Introduction

2. Quinolinones (8-hydroxycarbostyril)

3. Formamides

4. Saligenins

5. New head groups

6. Dual pharmacology

7. Conclusion References

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