7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase

Journal of Medicinal Chemistry

Volumn 41, Issue 13, 1998, Pages 2268-2277

  Duplantier, Allen J ^a   Andresen, Catharine J ^a   Cheng, John B ^a   Cohan, Victoria L ^a   Decker, Christian ^a   DiCapua, Frank M ^a   Kraus, Kenneth G ^a   Johnson, Kerry L ^a   Turner, Claudia R ^a   UmLand, John P ^a   Watson, John W ^a   Wester, Ronald T ^a   Williams, Alison S ^a   Williams, John A ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (CYCLOPENTYLOXY) 4 METHOXYPHENYL] 1 PHENYL 2 (4 PYRIDYL)ETHANE; 1 CYCLOPENTYL 3 ETHYL 6 (2 METHYLPHENYL) 7 OXO 4,5,6,7 TETRAHYDRO 1H PYRAZOLO[3,4 C]PYRIDINE; 3 ETHYL 1 (4 FLUOROPHENYL) 6 PHENYL 7 OXO 4,5,6,7 TETRAHYDRO 1H PYRAZOLO[3,4 C]PYRIDINE; 4 CYANO 4 [3 CYCLOPENTYLOXY 4 METHOXY PHENYL] 1 CYCLOHEXANECARBOXYLIC ACID; DYE; PHOSPHODIESTERASE INHIBITOR; PICLAMILAST; ROLIPRAM; UNCLASSIFIED DRUG;

AIRWAY OBSTRUCTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BRONCHODILATATION; CONFORMATIONAL TRANSITION; DRUG CONFORMATION; DRUG EFFECT; DRUG POTENCY; ENZYME INHIBITION; EOSINOPHIL; MONKEY; NEUTROPHIL; NONHUMAN; PROVOCATION TEST; STRUCTURE ACTIVITY RELATION;

AIRWAY OBSTRUCTION; ANIMALS; ANTI-ASTHMATIC AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BRONCHOALVEOLAR LAVAGE FLUID; CELL COUNT; CELL LINE; CYCLIC AMP; CYTOKINES; DIHYDROPYRIDINES; DRUG EVALUATION, PRECLINICAL; EOSINOPHILS; GUINEA PIGS; HUMANS; ISOENZYMES; MACACA FASCICULARIS; MOLECULAR CONFORMATION; NEUTROPHILS; OVALBUMIN; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PYRAZOLES; PYRROLIDINONES; ROLIPRAM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 15144343123     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9800090     Document Type: Article

References (19)

1. Palfreyman, M. N.; Souness, J. E. Phosphodiesterase Type IV inhibitors. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier Science, 1996; Vol. 33, pp 1-52.
2. Dent, G.; Giembycz, M. A. Selective Phosphodiesterase inhibitors in the Therapy of Asthma. Clin. Immunother. 1995, 3, 423-437.
3. Cavalla, D.; Frith, R. Phosphodiesterase IV inhibitors: Structural Diversity and Therapeutic Potential in Asthma. Curr. Med. Chem. 1995, 2, 561-572.
4. Nicholson, C. D.; Shahid, M. inhibitors of Cyclic Nucleotide Phosphodiesterase Isoenzymes - their Potential Utility in the Therapy of Asthma. Pulmonary Pharmacol. 1994, 7, 1-17.
5. Lombardo, L. J. Phosphodiesterase-IV inhibitors: Novel Therapeutics for the Treatment of inflammatory Diseases. Curr. Pharm. Des. 1995, 1, 255-268.
6. Muller, T.; Engels, P.; Fozard, J. R. Subtypes of the type 4 cAMP phosphodiesterases: Structure, regulation and selective inhibition. Trends Pharmacol. Sci. 1996, 17, 294-8.
7. Zeller, E.; Stief, H. J.; Pflug, B.; Sastre-y-Hernandez, M. Results of a Phase II Study of the Antidepressant Effect of Rolipram. Pharmacopsychiatry 1984, 17, 188-190.
8. Heaslip, R. J.; Evans, D. Y. Emetic, central nervous system and pulmonary activities of rolipram in the dog. Eur. J. Pharmacol. 1995, 286, 281-290.
9. 3H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret. J. Med. Chem. 1996, 39, 120-125.
10. Jonker, G. J.; Tijhuis, G. J.; Monchy, J. G. R. de RP 73401 (a Phosphodiesterase IV inhibitor) single dose does not prevent allergen induced broncho-constriction during the early phase reaction in asthmatics. Eur. Respir. J. 1996, 9 (Suppl. 23), 82S.
11. Harbinson, P. L.; MacLeod, D.; Hawksworth, R.; O'Toole, S.; Sullivan, P. J.; Heath, P.; Kilfeather, S.; Page, C. P.; Costello, J.; Holgate, S. T.; Lee, T. H. The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects. Eur. Respir. J. 1997, 10, 1008-1014.
12. Blatter, H. M. Certain tetrahydro pyrazolo-pyridine and pyrazolopiperidine derivatives. U.S. Patent 3 365 459, 1968.
13. Vyas, D. M.; Benigni, D.; Partyka, R. A.; Doyle, T. W. A Practical Synthesis of Mitomycin A and Its Analogs. J. Org. Chem. 1986, 51, 4307-9.
14. Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. Oxidative N-Dearylation of 2-Azetidinones. p-Anisidine as a Source of Azetidinone Nitrogen. J. Org. Chem. 1982, 47, 2765-8.
15. Reeves, M. L.; Leigh, B. K.; England, P. J. The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea pig cardiac ventricle. Biochem. J. 1987, 241, 535-541.
16. Turner, C. R.; Andresen, C. J.; Smith, W. B.; Watson, J. W. Effects of Rolipram on Responses to Acute and Chronic Antigen Exposure in Monkeys. Am. J. Respir. Crit. Care Med. 1994, 149, 1153-1159.
17. Goodford, P. J. A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules. J. Med. Chem. 1985, 28, 849-857.
18. Hone, S.; and Kita, H. CD11b/CD18 (Mac-1) Is Required for Degranulation of Human Eosinophils induced by Human Recombinant Granulocyte - Macrophage Colony - Stimulating Factor and Platelet-Activating Factor. J. Immunol. 1994, 152, 5457-5467.
19. Duplantier, A. J.; Kraus, K. G.; Marfat, A.; Chambers, R. J.; Grodski, A. Unpublished results.