Efficient conversion of a nonselective norepinephrin reuptake inhibitor into a dual muscarinic antagonist-β 2-agonist for the treatment of chronic obstructive pulmonary disease

Journal of Medicinal Chemistry

Volumn 54, Issue 19, 2011, Pages 6998-7002

  Osborne, Rachel ^a   Clarke, Nick ^a   Glossop, Paul ^a   Kenyon, Amy ^a   Liu, Hao ^a   Patel, Sheena ^a   Summerhill, Susan ^a   Jones, Lyn H ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; G PROTEIN COUPLED RECEPTOR; INDAZOLE DERIVATIVE; TOLTERODINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRONCHOSPASM; CHRONIC OBSTRUCTIVE LUNG DISEASE; DRUG CONJUGATION; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; GUINEA PIG; HUMAN; HUMAN CELL; NONHUMAN; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION; TRACHEA;

ADRENERGIC BETA-2 RECEPTOR AGONISTS; ADRENERGIC UPTAKE INHIBITORS; ANIMALS; BRONCHOCONSTRICTION; BRONCHODILATOR AGENTS; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; GUINEA PIGS; HUMANS; MICROSOMES, LIVER; MODELS, MOLECULAR; MUSCARINIC ANTAGONISTS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RECEPTOR, MUSCARINIC M3; STRUCTURE-ACTIVITY RELATIONSHIP; TRACHEA;

EID: 80053923217     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2007535     Document Type: Article

References (19)

1. http://www.who.int/respiratory/copd/en/.
2. Cazzola, M.; Molimard, M. The scientific rationale for combining long-acting β-2 agonists and muscarinic antagonists in COPD Pulm. Pharmacol. Ther. 2010, 23, 257-267
3. Welte, T. Optimising treatment for COPD-new strategies for combination therapy Int. J. Clin. Pract. 2009, 63, 1136-1149
4. Ray, N.; Alcaraz, L. Muscarinic antagonist-β-adrenergic agonist dual pharmacology molecules as bronchodilators: a patent review Expert Opin. Ther. Pat. 2009, 19, 1-12
5. Cazzola, M.; Matera, M. Novel long-acting bronchodilators for COPD and asthma Br. J. Pharmacol. 2008, 155, 291-299
6. Jones, L. H.; Baldock, H.; Bunnage, M.; Burrows, J.; Clarke, N.; Coghlan, M.; Entwistle, D.; Fairman, D.; Feeder, N.; Fulton, C.; Hilton, L.; James, K.; Jones, R.; Kenyon, A.; Marshall, S.; Newman, S.; Osborne, R.; Patel, S.; Selby, M.; Stuart, E.; Trevethick, M.; Wright, K.; Price, D. Inhalation by design: dual pharmacology β-2 agonists/M3 antagonists for the treatment of COPD Bioorg. Med. Chem. Lett. 2011, 21, 2759-2763
7. Hughes, A.; Chin, K.; Dunham, S.; Jasper, J.; King, K.; Lee, T.; Mammen, M.; Martin, J.; Steinfeld, T. Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules Bioorg. Med. Chem. Lett. 2011, 21, 1354-1358
8. Mammen, M.; Dunham, S.; Hughes, A.; Tae, W.; Husfeld, C.; Stangeland, E. Biphenyl Derivatives. US 20040167167, 2004.
9. Jones, L. H.; Lunn, G.; Price, D. Sulfonamide Derivatives as Adrenergic Agonists and Muscarinic Antagonists. WO 2008041095, 2008.
10. http://www.cerep.fr/Cerep/Users/pages/ProductsServices/catalog.asp.
11. Schelkun, R. M.; Yuen, P.-W. Therapeutic Pyrazolo[3,4- b ]pyridines and Indazoles. WO 2006056873, 2006.
12. Peters, J.-U.; Schnider, P.; Mattei, P.; Kansy, M. Pharmacological promiscuity: dependence on compound properties and target specificity in a set of recent Roche compounds ChemMedChem 2009, 4, 680-686
13. Lainé, D. I.; McCleland, B.; Thomas, S.; Neipp, C.; Underwood, B.; Dufour, J.; Widdowson, K. L.; Palovich, M. R.; Blaney, F. E.; Foley, J. J.; Webb, E. F.; Luttman, M. A.; Burman, M.; Belmonte, K.; Salmon, M. Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists J. Med. Chem. 2009, 52, 2493-2505
14. Kosutic-Hulita, N.; Zegarac, M. Tolterodinium (+)-(2 R,3 R)-hydrogen tartrate Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2005, 61, o171-o173
15. Carter, J. P.; Noronha-Blob, L.; Audia, V. H.; Dupont, A. C.; McPherson, D. W.; Natalie, K. J., Jr.; Rzeszotarski, W. J.; Spagnuolo, C. J.; Waid, P. P.; Kaiser, C. Analogs of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds J. Med. Chem. 1991, 34, 3065-3074
16. Druzgala, P. Novel Anticholinergic Compounds for the Treatment of Incontinence and Other Disorders. US 20020169208, 2002.
17. 2- adrenoceptor agonist (MABA) that binds in a bimodal and multivalent manner Mol. Pharmacol. 2011, 79, 389-399
18. Summerhill, S.; Stroud, T.; Nagendra, R.; Perros-Huguet, C.; Trevethick, M. A cell-based assay to assess the persistence of action of agonists acting at recombinant human β2 adrenoceptors J. Pharmacol. Toxicol. Methods 2008, 58, 189-197
19. Watson, J.; Strawbridge, M.; Brown, R.; Campany, K.; Coghlan, M.; Trevethick, M. Offset rates of tiotropium and ipratropium at human recombinant muscarinic M1-M5 receptors using a dilution-offset methodology Fundam. Clin. Pharmacol. 2008, 22 (Suppl. 2) 78