Novel cyclic compounds as potent phosphodiesterase 4 inhibitors

Journal of Medicinal Chemistry

Volumn 41, Issue 22, 1998, Pages 4216-4223

  He, Wei ^a   Huang, Fu Chih ^a   Hanney, Barbara ^a   Souness, John ^a   Miller, Bruce ^a   Liang, Guyan ^a   Mason, Jon ^a,b   Djuric, Stevan ^a,c  

^a SW 8 Rhone Poulenc Rorer Ctrl Res ^*  (United States)

^b BRISTOL MYERS SQUIBB   (United States)

^c ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,3 INDANDIONE DERIVATIVE; LIPOPOLYSACCHARIDE; PHOSPHODIESTERASE IV INHIBITOR; PICLAMILAST; ROLIPRAM; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN MEMBRANE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DOG; DRUG POTENCY; DRUG SYNTHESIS; ENDOTOXEMIA; ENZYME INHIBITION; GUINEA PIG; INTRAVENOUS DRUG ADMINISTRATION; MOLECULAR MODEL; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION; VOMITING;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BENZAMIDES; BRAIN; DOGS; ENDOTOXEMIA; FEMALE; GUINEA PIGS; LIPOPOLYSACCHARIDES; MACROPHAGES, PERITONEAL; MALE; MICE; MICE, INBRED BALB C; MODELS, MOLECULAR; PHOSPHODIESTERASE INHIBITORS; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA; VOMITING;

EID: 0032561213     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970575f     Document Type: Article

References (39)

1. Beutler, B.; Cerami, A. Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 1986, 320, 584-589.
2. (a) Strieter, R. M.; Remick, D. G.; Ward, P. A.; Spengler, R. N.; Lynch, J. F.; Larrick, J.; Kunkel, S. L. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem. Biophy. Res. Commun. 1988, 155, 1230-1236.
3. (b) Taffet, S. M.; Singhel, K. J.; Overholtzer, J. F.; Shurtleff, S. A. Regulation of tumor necrosis factor expression in a macrophage-like cell line by lipopolysaccharide and cyclic AMP. Cell. Immunol. 1989, 120, 291-300.
4. (a) Dulpantier, A. J.; Cheng, J. B. Emerging opportunities in the treatment of asthma and allergy. Annu. Rep. Med. Chem. 1994, 29, 73-81.
5. (b) Nicholson, C. D.; Shahid, M. Inhibitors of cyclic nucleotide phosphodiesterase isozymes -their potential utility in the therapy of asthma. Pulmonary Pharmacol. 1994, 7, 1-17.
6. (c) Torphy, T. J.; Livi, G. P.; Christensen, S. B. Novel phosphodiesterase inhibitors for the therapy of asthma. Drug News Perspect. 1993, 6, 203-214.
7. (d) Lowe, J. A., III; Cheng, J. B. The PDE IV family of calcium-independent phosphodiesterase enzymes. Drugs Future 1994, 29, 73-81.
8. (e) Palfreyman, M. N.; Souness, J. E. Phosphodiesterase type IV inhibitors. Prog. in Med. Chem. 1996, 33, 1-52.
9. Schwabe, U.; Miyake, M.; Ohga, Y.; Daly, J. 4-(3-Cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK62711): A potent inhibitor of adenosine cyclic 3′,5′-monophosphophate phosphodiesterase in homogenates and tissue slices from rat brain. Mol. Pharmacol. 1976, 28, 900-910.
10. Zeller, E.; Stief, H. J.; Pflug, B.; Satre, Y.; Hernandez, M. Results of a phase II study of the antidepressant effect of rolipram. Pharmacopsychiatry 1984, 17, 188-190.
11. (a) Ashton, M. J.; Cook, D. C.; Fenton, G.; Karlsson, J. A.; Palfreyman, M. N.; Raeburn, D.; Ratcliffe, A. J.; Souness, J. E.; Thurairatnam, S.; Vicker, N. Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenamides and analogues. J. Med. Chem. 1994, 37, 1696-1703.
12. 3H]rolipram binding activity and their relationship to emetic behavior in the ferret. J. Med. Chem. 1996, 39, 120-125.
13. 3H]rolipram binding site: 3-norbornyloxy-4-methoxyphenylmethylene oxindoles. Bioorg. Med. Chem. Lett. 1995, 5, 1965-1968.
14. 3H]rolipram binding site. Bioorg. Med. Chem. Lett. 1995, 5, 1969-1972.
15. (e) Dal Piaz, V.; Giovannoni, M. P.; Castellana, C. Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase IV inhibitors. J. Med. Chem. 1997, 40, 1417-1421.
16. (f) Lampe, J. W.; Chou, Y.-L.; Hanna, R. G.; Di Meo, S. V.; Erhardt, P. W.; Hagedorn, A. A., III; Ingebretesen, W. R.; Cantor, E. (Imidazolylphenyl)pyrrol-2-one inhibitor of cardiac cAMP phosphodiesterase. J. Med. Chem. 1993, 36, 1041-1047.
17. (g) Brackeen, M. F.; Cowan, D. J.; Stfford, J. A.; Schoenen, J. M.; Domanico, P. L.; Rose, D.; Strickland, A. B.; Verghese, M.; Feldman, P. L. Design and synthesis of conformationally constrained analogues of 4-(3-butoxy-4-methoxy)imidazolidin-2-one (Ro 20-1724) as potent inhibitors of cAMP-specific phosphodiesterase. J. Med. Chem. 1995, 38, 4848-4854.
18. (a) Muller, T.; Engels, P.; Fozard, J. R. Subtypes of the type 4 cAMP phospho- diesterase: structure, regulation and selective inhibition. Trends Pharmacol. Sci. 1996, 17, 294-298.
19. 3H]-(-)-rolipram binding by selective inhibitors. Biochem. J. 1996, 318, 425-436.
20. (a) Schmiechen, R.; Schneider, H. H.; Watchtel, H. Close correlation between behavioural response and binding in vivo for inhibitors of the rolipram-sensitive phosphodiesterase. Psychopharmacology 1990, 102, 17-20.
21. (b) Schneider, H. H.; Schmiechen, R.; Brezinski, M.; Seidler, J. Stereospecific binding of the antidepressant rolipram to brain protein structures. Eur. J. Pharmacol. 1986, 127, 105-115.
22. 3H]rolipram binding, Biochem. Pharmacol. 1996, 51, 949-956.
23. (d) Barnett, M. S.; Grous, M.; Cieslinski, L. B.; Burman, M.; Christensen, S. B.; Torphy, T. J. Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: correlation between function and interaction with a high-affinity rolipram binding site. J. Pharmacol. Exp. Ther. 1995, 273, 1396-1402.
24. (a) Warrellow, G. J.; Alexander, R. P.; Boyd, E. C.; Eaton, M. A.; Head, J. C.; Higgs, G. A. The design of an orally active PDE IV inhibitor (CDP 840) for asthma. 8th RSC-SCI Medicinal Chemistry Symposium, Cambridge, U.K., 1995.
25. (b) Hughes, B. CDP 840. 2nd World Congress on Inflammation, Brighton, U.K., 1995.
26. (c) Hughes, B. Fourth Annual Midwest Meeting of the Inflammation Research Association, Chicago, IL, 1996.
27. (d) Hughes, B.; Howat, D.; Lisle, H. M.; James, T.; Gozzard, N.; Blease, K.; Hughes, P.; Kingaby, R.; Warrellow, G.; Alexander, R.; Head, J.; Boyd, E.; Eaton, M.; Perry, M.; Wales, M.; Smith, B.; Owens, R.; Catterall, C.; Lumb, S.; Russell, A.; Allen, R.; Merriman, M.; Bloxham, D.; Higgs, G. The inhibition of antigen-induced eosinophilia and bronchoconstriction by CDP840, a novel stereoselective inhibitor of phosphodiesterase type 4. Br. J. Pharmacol. 1996, 118, 1183-1191.
28. Unpublished results of Dagenham Research Centre, RPR, U.K.
29. Mitsunobu, O.; Yamada, M. Preparation of esters of carboxylic and phosphoric acid via quaternary phosphonium salts. Bull. Chem. Soc. Jpn. 1967, 40, 2380-238.
30. Johnson, J. R. The Perkin reaction and related reactions. Org. React. 1942, 1, 211-256.
31. (a) Molnar-Kimber, K. L.; Yonno, L.; Heaslip, R. J.; Weichman, B. M. Differential regulation of TNF-α and IL-1β production from endotoxin stimulated human monocytes by phosphodiesterase inhibitors. Mediat. Inflam. 1992, 1, 411-417.
32. (b) Feldman, P. L.; Brackeen, M. F.; Cowan, D. J.; Marron, B. E.; Schoenen, F. J.; Stafford, J. A.; Suh, E. M.; Domanico, P. L.; Rose, D.; Leesnitzer, M. A.; Brawley, E. S.; Strickland, A. B.; Verghese, M. W.; Connolly, K. M.; Batoman-Fite, R.; Noel, L. S.; Sekut, L.; Stimpson, S. A. Phosphodiesterase type IV inhibition. Structure - activity relationships of 1,3-disubstituted pyrrolidines. J. Med. Chem. 1995, 38, 1505-1510.
33. (c) Souness, J. E.; Griffin, M.; Maslen, C.; Ebsworth, K.; Scott, L. C.; Pollock, K.; Palfreyman, M. N.; Karlsson, J.-A. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNFα generation from human monocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer. Br. J. Pharmacol. 1996, 118, 649-658.
34. For the therapeutic ratio of RP 73401 administered orally: Escott, K. J.; McMillan, S. J.; Birrell, M.; Webber, S. E.; Souness, J. E.; Maslen, C.; Temple, R.; Iqbal, S.; Mariucci, M.; Rose, J.; Geiger, L. E.; Thurairatnam, S.; Bower, S.; Aldous, D.; Sargent, C. A. Pharmacological profiling of phosphodiesterase 4 (PDE4) inhibitors and analysis of the therapeutic ratio in rats and dogs. Br. J. Pharmacol. 1998, 123, 40.
35. (a) Jezequel, S. G. Central nervous system penetration of drugs: importance of physicochemical properties. In Progress in Drug Metabolism; Gibson, G. G., Ed.; Taylor & Francis: London, U.K., 1992; Vol. 13, pp 141-178.
36. (b) Lin, J. H.; Lu, A. Y. H. Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol. Rev. 1997, 49, 403-449.
37. Menard, M.; Erichomovitch, L.; La Brooy, M.; Chubb, F. L. Quelques metabolites possibles de la thalidomide. Can. J. Chem. 1963, 41, 1722-1724.
38. Turner, N. C.; Wood, L. J.; Burns, F. M.; Gueremy, T.; Souness, J. E. The effect of cyclic AMP and cyclic GMP phosphodiesterase inhibitors on the Superoxide burst of guinea-pig peritoneal macrophages. Br. J. Pharmacol. 1993, 108, 876-883.
39. Thompson, W. J.; Terasaki, W.; Epstein, P. M.; Strada, S. J. Assay of cyclic nucleotide phosphodiesterase and resolution of multiple molecular forms of the enzyme. Adv. Cycl. Nucleotide Res. 1979, 10, 69-92.