Substituted (Pyridylmethoxy)naphthalenes as potent and orally active 5- Lipoxygenase inhibitors: Synthesis, biological profile, and pharmacokinetics of L-739,010

Journal of Medicinal Chemistry

Volumn 40, Issue 18, 1997, Pages 2866-2875

  Hamel, Pierre ^a   Riendeau, Denis ^a   Brideau, Christine ^a   Chan, Chi Chung ^a   Desmarais, Sylvie ^a   Delorme, Daniel ^a,b   Dubé, Daniel ^a   Ducharme, Yves ^a   Ethier, Diane ^a   Grimm, Erich ^a   Falgueyret, Jean Pierre ^a   Guay, Jocelyne ^a   Jones, Tom R ^a   Kwong, Elizabeth ^a   McAuliffe, Malia ^a   McFarlane, Cyril S ^a   Piechuta, Hanna ^a   Roumi, Marie ^a   Tagari, Philip ^a   Young, Robert N ^a   Girard, Yves ^a   more..

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

^b Astra Pain Research Unit   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 [6 [7 CYANO 5 (3 FURYL) 2 NAPHTHOXYMETHYL] 2 PYRIDYL] 3 HYDROXY 6,8 DIOXABICYCLO[3.2.1]OCTANE; LEUKOTRIENE B4; LIPOXYGENASE INHIBITOR;

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRONCHOSPASM; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; ENZYME INHIBITION; INTRAVENOUS DRUG ADMINISTRATION; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; SHEEP; SQUIRREL MONKEY; STRUCTURE ACTIVITY RELATION;

ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; ASCARIS; BIOLOGICAL AVAILABILITY; BRONCHODILATOR AGENTS; DOGS; DYSPNEA; HUMANS; INFLAMMATION; LIPOXYGENASE INHIBITORS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; NAPHTHALENES; NEMATODE INFECTIONS; PYRIDINES; RATS; RECOMBINANT PROTEINS; SAIMIRI; SHEEP; SPODOPTERA; TRANSFECTION;

EID: 15644372739     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970046b     Document Type: Article

References (29)

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3. 5-LO or FLAP inhibitors, recent clinical results: (a) Israel, E.; Rubin, P.; Kemp, J. P.; Grossman, J.; Pierson, W.; Siegel, S. C.; Tinkelman, D.; Murray, J. J.; Busse, W.; Segal, A. T.; Fish, J.; Kaiser, H. B.; Ledford, D.; Wenzel, S.; Rosenthal, R.; Cohn, J.; Lanni, C.; Perlman, H.; Karahalios, P.; Drasen, J. M. The Effect of Inhibition of 5-Lipoxygenase by Zileuton in Mild-to-Moderate Asthma. Ann. Intern. Med. 1993, 119, 1059-1066. (b) Friedman, B. S.; Bel, E. H.; Buntinx, A.; Tanaka, W.; Han, Y. H.; Shingo, S.; Spector, R.; Sterk, P. Oral Leukotriene Inhibitor (MK-886) Blocks Allergen-Induced Airway Responses. Am. Rev. Respir. Dis. 1993, 147, 839-844. (c) Diamant, Z.; Timmers, M. C.; van der Veen, H.; Friedman, B. S.; De Smet, M.; Depré, M.; Hilliard, D.; Bel, E.; Sterk, P. J. The Effect of MK-0591, a Novel 5-Lipoxygenase Activating Protein Inhibitor, on Leukotriene Biosynthesis and Allergen-Induced Airway Responses In Asthmatic Subjects In Vivo. J. Allergy Clin. Immunol. 1995, 95, 42-51.
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5. LTD4 antagonists, recent clinical results: (a) Margolskee, D.; Bodman, S.; Dockborn, R.; Israel, E.; Kemp, J.; Mansmann, H.; Minotti, D. A.; Spector, S.; Stricker, W.; Tinkelman, D.; Townley, R.; Winder, J.; Williams, V. The Therapeutic Effects of MK-571. A Potent and Selective LTD4 Receptor Antagonist in Patients with Chronic Asthma. J. Clin. Allergy Immunol. 1991, 87, 309. (b) Impens, N.; Reiss, T. F.; Teahan, J. A.; Desmet, M.; Rossing, T. H.; Shingo, S.; Zhang, J.; Schandevyl, W.; Verbesselt, R.; Dupont, A. G. Acute Bronchodilation with an Intravenously Administered Leukotriene D4 Antagonist MK-679. Am. Rev. Respir. Dis. 1993, 147, 1442-1446. (c) Reiss, T. F.; Bronsky, E.; Hendeles, L.; Hill, J.; Harman, E.; Guerreiro, D.; Zhang, J. MK-0476, A Potent Leukotriene D4 Receptor Antagonist, Inhibits Exercise Induced Bronchoconstriction is Asthmatics at the End of a Once Daily Dosing Interval. Am. J. Respir. Crit. Care Med. 1995, 151, A377. (d) Dahlen, B.; Zetterstrom, O.; Bjorck, T.; Dahlen, S. E. The Leukotriene-Antagonist ICI-204,219 Inhibits the Early Airway Reaction to Cumulative Bronchial Challenge with Allergen in Atopic Asthmatics. Eur. Respir. J. 1994, 7, 324-331. (e) Taniguchi, Y.; Tamura, G.; Honma, M.; Aizawa, T.; Maruyama, N.; Shirato, K.; Takishima, T. The Effect of an Oral Leukotriene Antagonist, ONO-1078, on Allergen-Induced Immediate Bronchoconstriction in Asthmatic Subjects. J. Allergy Clin. Immunol. 1993, 92, 507-512.
6. LTD4 antagonists, recent clinical results: (a) Margolskee, D.; Bodman, S.; Dockborn, R.; Israel, E.; Kemp, J.; Mansmann, H.; Minotti, D. A.; Spector, S.; Stricker, W.; Tinkelman, D.; Townley, R.; Winder, J.; Williams, V. The Therapeutic Effects of MK-571. A Potent and Selective LTD4 Receptor Antagonist in Patients with Chronic Asthma. J. Clin. Allergy Immunol. 1991, 87, 309. (b) Impens, N.; Reiss, T. F.; Teahan, J. A.; Desmet, M.; Rossing, T. H.; Shingo, S.; Zhang, J.; Schandevyl, W.; Verbesselt, R.; Dupont, A. G. Acute Bronchodilation with an Intravenously Administered Leukotriene D4 Antagonist MK-679. Am. Rev. Respir. Dis. 1993, 147, 1442-1446. (c) Reiss, T. F.; Bronsky, E.; Hendeles, L.; Hill, J.; Harman, E.; Guerreiro, D.; Zhang, J. MK-0476, A Potent Leukotriene D4 Receptor Antagonist, Inhibits Exercise Induced Bronchoconstriction is Asthmatics at the End of a Once Daily Dosing Interval. Am. J. Respir. Crit. Care Med. 1995, 151, A377. (d) Dahlen, B.; Zetterstrom, O.; Bjorck, T.; Dahlen, S. E. The Leukotriene-Antagonist ICI-204,219 Inhibits the Early Airway Reaction to Cumulative Bronchial Challenge with Allergen in Atopic Asthmatics. Eur. Respir. J. 1994, 7, 324-331. (e) Taniguchi, Y.; Tamura, G.; Honma, M.; Aizawa, T.; Maruyama, N.; Shirato, K.; Takishima, T. The Effect of an Oral Leukotriene Antagonist, ONO-1078, on Allergen-Induced Immediate Bronchoconstriction in Asthmatic Subjects. J. Allergy Clin. Immunol. 1993, 92, 507-512.
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