Synthesis and structure-activity relationships of long-acting β2 adrenergic receptor agonists incorporating metabolic inactivation: An antedrug approach

Journal of Medicinal Chemistry

Volumn 53, Issue 11, 2010, Pages 4522-4530

  Procopiou, Panayiotis A ^a   Barrett, Victoria J ^a   Bevan, Nicola J ^a   Biggadike, Keith ^a   Box, Philip C ^a   Butchers, Peter R ^a   Coe, Diane M ^a   Conroy, Richard ^a   Emmons, Amanda ^a   Ford, Alison J ^a   Holmes, Duncan S ^a   Horsley, Helen ^a   Kerr, Fern ^a   Li Kwai Cheung, Anne Marie ^a   Looker, Brian E ^a   Mann, Inderjit S ^a   McLay, Iain M ^a   Morrison, Valerie S ^a   Mutch, Peter J ^a   Smith, Claire E ^a   Tomlin, Paula ^a   more..

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 [[6 [[2 [[(2,6 DICHLOROPHENYL)METHYL]OXY]ETHYL]OXY]HEXYL]AMINO] 1 HYDROXYETHYL] 2 (HYDROXYMETHYL)PHENOL; BETA 1 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA 3 ADRENERGIC RECEPTOR; CYCLIC AMP; ISOPRENALINE; OXAZOLIDINONE DERIVATIVE; SALIGENIN; SALMETEROL; UNCLASSIFIED DRUG;

ALKYLATION; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTHMA; CHO CELL; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; GUINEA PIG; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIVER MICROSOME; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STRUCTURE ACTIVITY RELATION; TRACHEA;

ADRENERGIC BETA-AGONISTS; ANIMALS; BENZYL ALCOHOL; BENZYL ALCOHOLS; CHLOROBENZENES; CHO CELLS; CRICETINAE; CRICETULUS; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RATS; RECEPTORS, ADRENERGIC, BETA-2; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77953215962     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100326d     Document Type: Article

References (35)

1. Barnes, P. J. Immunology of asthma and chronic obstructive pulmonary disease Nature Rev. Immunol. 2008, 8, 183-192
2. Barnes, P. J. Efficacy of inhaled corticosteroids in asthma J. Allergy Clin. Immunol. 1998, 102, 531-538
3. Boushey, H. A. Effects of inhaled corticosteroids on the consequences of asthma J. Allergy Clin. Immunol. 1998, 102, S5-S16
4. Johnson, M. Salmeterol Med. Res. Rev. 1995, 15, 225-257
5. 2- Agonist besides Formoterol in Patients with Asthma? Respiration 2001, 68, 432-437
6. Johnson, M. The β-adrenoceptor Am. J. Respir. Crit. Care Med. 1998, 158 (5 Pt 3) S146-S153
7. 2 adrenoceptor agonist with a 24 h duration of action J. Pharmacol. Exper. Ther. 2006, 317, 762-770
8. 2-Adrenoceptor Agonists Annu. Rep. Med. Chem. 2006, 41, 237-248
9. 2- adrenoreceptor agonists Bioorg. Med. Chem. Lett. 2007, 17, 4012-4015
10. 2- adrenoceptor agonists for the treatment of asthma and COPD Bioorg. Med. Chem. Lett. 2007, 17, 6188-6191
11. 2-adrenoreceptor agonists Bioorg. Med. Chem. Lett. 2008, 18, 1280-1283
12. 2 Adrenergic Receptor Agonists Incorporating Arylsulfonamide Groups J. Med. Chem. 2009, 52, 2280-2288
13. 2-adrenoceptor agonists with a long duration of action Bioorg. Med. Chem. Lett. 2009, 19, 5237-5240
14. 2-adrenoceptor agonists Bioorg. Med. Chem. Lett. 2009, 19, 6640-6644
15. 2-adrenoceptor agonist with a 24 h bronchodilatory efficacy Bioorg. Med. Chem. Lett. 2010, 20, 1410-1414
16. Bennett, J. A.; Harrison, T. W.; Tattersfield, A. E. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects Eur. Respir. J. 1999, 13, 445-448
17. Lee, H. J.; Ko, D.-H.; McLean, H. M. Recent Advances in Prodrugs and Antedrugs Curr. Opin. Drug Discovery Dev. 1998, 1, 235-244
18. Bodor, N.; Buchwald, P. Drug Targeting via Retrometabolic Approaches Pharmacol. Ther. 1997, 76, 1-27 (Pubitemid 28078557)
19. Procopiou, P. A.; Biggadike, K.; English, A. F.; Farrell, R. M.; Hagger, G. N.; Hancock, A. P.; Haase, M. V.; Irving, W. R.; Sareen, M.; Snowden, M. A.; Solanke, Y. E.; Tralau-Stewart, C. J.; Walton, S. E.; Wood, J. A. Novel Glucocorticoid Antedrugs Possessing a 17β-(γ-Lactone) Ring J. Med. Chem. 2001, 44, 602-612
20. Biggadike, K.; Angell, R. M.; Burgess, C. M.; Farrell, R. M.; Hancock, A. P.; Harker, A. J.; Irving, W. R.; Ioannou, C.; Procopiou, P. A.; Shaw, R. E.; Solanke, Y. E.; Singh, O. M. P.; Snowden, M. A.; Stubbs, R. J.; Walton, S. E.; Weston, H. E. Selective Plasma Hydrolysis of Glucocorticoid γ-Lactones and Cyclic Carbonates by the Enzyme Paraoxonase: An Ideal Plasma Inactivation Mechanism J. Med. Chem. 2000, 43, 19-21
21. Biggadike, K.; Lynn, S. M.; Procopiou, P. A.; Shaw, R. E.; Williamson, C. Novel Glucocorticoid Antedrugs Possessing a C16,17-Fused γ-Lactone Ring J. Chem. Soc., Perkin Trans. 1 2000, 813-818
22. Angell, R. A.; Biggadike, K.; Farrell, R. M.; Flack, S. S.; Hancock, A. P.; Irving, W. R.; Lynn, S. M.; Procopiou, P. A. Novel Glucocorticoid Antedrugs Possessing a 21-(γ-Lactone) Ring J. Chem. Soc., Perkin Trans. 1 2002, 831-839
23. Manchee, G. R.; Barrow, A.; Kulkarni, S.; Palmer, E.; Oxford, J.; Colthup, P. V.; Maconochie, J. G.; Tarbit, M. H. Disposition of salmeterol xinafoate in laboratory animals and humans Drug Metab. Dispos. 1993, 21, 1022-1028 (Pubitemid 23348338)
24. Manchee, G. R.; Eddershaw, P. J.; Ranshaw, L. E. The aliphatic oxidation of salmeterol to α-hydroxysalmeterol in human liver microsomes is catalyzed by CYP3A Drug Metab. Dispos. 1996, 24, 555-559
25. Biggadike, K; Angell, R. M.; Procopiou, P. A.; Farrell, R. M.; Usha, V.; Ramesh, U. V.; Holmes, D. S. Patent WO 9901467 A2, 14 Jan 1999.
26. Wallis, C. J. Salbutamol, salmeterol: a chemist's perspective. Actual. Chim. Ther. 20é série 1993, 265-292.
27. Coe, D. M.; Perciaccante, R.; Procopiou, P. A. Potassium trimethylsilanolate induced cleavage of 1,3-oxazolidin-2-and 5-ones, and application to the synthesis of (R)-salmeterol Org. Biomol. Chem. 2003, 1, 1106-1111
28. Ranshaw, L.; Mutch, P. J.; Smith, C. E. unpublished results.
29. 2 adrenoceptor agonist salmeterol Br. J. Pharmacol. 1993, 108, 507-515
30. Box, P. C.; Coe, D. M.; Looker, B. E.; Procopiou, P. A. Patent WO03024439 A1, 27 March 2003.
31. Ford, A. J.; Barrett, V. J.; Bevan, N. J.; Butchers, P. R.; Emmons, A. Unpublished Results.
32. 2 adrenoceptor agonist (LABA), at single doses of 25, 50 and 100 μg demonstrates prolonged bronchodilation and a favourable safety and tolerability profile in asthmatic patients. International Conference, American Thoracic Society, New Orleans, LA, May 14-19, 2010, Abstract 289.
33. 2-Adrenergic G Protein-Coupled Receptor Science 2007, 318, 1258-1265
34. 2-Adrenergic Receptor Function Science 2007, 318, 1266-1273
35. 2 adrenergic G-protein-coupled receptor Nature 2007, 450, 383-388