Palladium-catalyzed cross-coupling reactions for the synthesis of 6,8- disubstituted 1,7-naphthyridines: A novel class of potent and selective phosphodiesterase type 4D inhibitors

Journal of Medicinal Chemistry

Volumn 43, Issue 4, 2000, Pages 675-682

  Hersperger, Rene ^a   Bray French, Katharine ^b   Mazzoni, Lazzaro ^a   Müller, Thomas ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b RCC Registration and Consulting C   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

4 [8 (3 NITROPHENYL) [1,7]NAPHTHYRIDIN 6 YL]BENZOIC ACID; NAPHTHYRIDINE DERIVATIVE; PALLADIUM; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTHMA; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; EOSINOPHIL; HUMAN; HUMAN CELL; LUNG LAVAGE; NONHUMAN; RAT;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; ADMINISTRATION, ORAL; ANIMALS; ANTI-ASTHMATIC AGENTS; ASTHMA; BENZOIC ACIDS; BRONCHOALVEOLAR LAVAGE FLUID; CATALYSIS; ENZYME INHIBITORS; EOSINOPHILS; HUMANS; MALE; NAPHTHYRIDINES; PALLADIUM; RATS; RESPIRATORY BURST; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033995031     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991094u     Document Type: Article

References (28)

1. Teixeira, M. M.; Gristwood, R. W.; Cooper N.; Hellewell, P. G. Phosphodiesterase (PDE) 4 inhibitors: antiinflammatory drugs of the future? Trends Pharmacol. Sci. 1997, 18, 164-170.
2. Phosphodiesterase Inhibitors; Schudt, C., Dent, G., Rabe, K. F., Eds.; Academic Press: London, 1996.
3. Shire, M. G.; Muller, G. W. Exp. Opin. Ther. Patents 1998, 8, 531-544. Norman, P. PDE4 inhibitors 1998. Exp. Opin. Ther. Patents 1998, 8, 771-784.
4. Shire, M. G.; Muller, G. W. Exp. Opin. Ther. Patents 1998, 8, 531-544. Norman, P. PDE4 inhibitors 1998. Exp. Opin. Ther. Patents 1998, 8, 771-784.
5. Beavo, J. A. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev. 1995, 75, 725-48. See also: Beavo, J. A. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7071-7076.
6. Beavo, J. A. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol. Rev. 1995, 75, 725-48. See also: Beavo, J. A. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7071-7076.
7. Müller, T.; Engels, P.; Fozard, J. R. Subtypes of the type 4 cAMP phosphodiesterases: structure, regulation and selective inhibition. Trends Pharmacol. Sci. 1996, 17, 294-298.
8. Barnette, M. S.; Christensen, S. B.; Underwood, D. C.; Torphy, T. J. Phosphodiesterase 4: Biological underpinnings for the design of improved inhibitors. Pharmacol. Rev. Commun. 1996, 8, 65-73.
9. Christensen, S. B.; Guider, A.; Forster, C. J.; Gleason, J. G.; Bender, P. E.; Karpinski, J. M.; DeWolf, W. E. Jr.; Barnette, M. S.; Underwood, D. C.; Griswold, D. E.; Cieslinski, L. B.; Burman, M.; Bochnowicz, S.; Osborn, R. R.; Manning, C. D.; Grous, M.; Hillegas, L. M.; Bartus, J. O.; Ryan, M. D.; Eggleston, D. S.; Haltiwanger, R. C.; Torphy, T. J. 4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma J. Med. Chem. 1998, 41, 821-835.
10. Murdoch, R. D.; Cowley, H.; Upward, J.; Webber, D.; Wyld, P. The safety and tolerability of Ariflo (SB207499), a novel and selective phospodiesterease 4 inhibitor, in healthy male volunteers. Am. J. Respir. Crit. Care Med. 1998, 157, Poster L57.
11. Alvarez, R.; Sette, C.; Yang, D.; Eglen, R. M.; Wilhelm, R.; Shelton, E. R.; Conti, M. Activation and selective inhibition of a cyclic AMP-specific phosphodiesterase, PDE-4D3. Mol. Pharmacol. 1995, 48, 616-622.
12. Naef, R. Isoquinolines for asthma therapy. Ger. Offen. DE 4438737 A1 950511.
13. Stille, J. K. The palladium-catalyzed cross-coupling reactions of organotin reagents with organic electrophiles. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524. Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457-2483.
14. Stille, J. K. The palladium-catalyzed cross-coupling reactions of organotin reagents with organic electrophiles. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524. Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457-2483.
15. Robinson, D. S. Eosinophils and asthma. What do measurements tell us? Clin. Exp. Allergy 1995, 25, 795-798.
16. Fife, W. K. Regioselective cyanation of pyridine 1-oxides with trimethylsilanecarbonitrile: a modified Reissert-Henze reaction. J. Org. Chem. 1983, 48, 1377-1379.
17. Danieli, R.; Ricci, A. Improvements in the synthesis of 2,7- and 2,6-naphthyridines Synthesis 1973, 46-47.
18. Tan, R.; Taurins, A. A new synthesis of 1,7-naphthyridine. Tetrahedron Lett. 1966, 12, 1233-1237.
19. Kotsuki, H.; Datta, P. K.; Hayakawa, H.; Suenaga, H. An efficient procedure for palladium-catalyzed reduction of aryl/enol triflates. Synthesis 1995, 1348-1350.
20. Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Palladium-catalyzed carbonylation of aryl triflates. Synthesis of arenecarboxylic acid derivatives from phenols. Tetrahedron Lett. 1986, 27, 3931-3934.
21. Torphy, T. J.; Stadel, J. M.; Burman, M.; Cieslinski, L. B.; McLaughlin, M. M.; White, J. R.; Livi, G. P. Coexpression of human cAMP-specific phosphodiesterase activity and high affinity rolipram binding in yeast. J. Biol. Chem. 1992, 267, 1798-1804. 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. Torphy, T. J.; Stadel, J. M.; Burman, M.; Cieslinski, L. B.; McLaughlin, M. M.; White, J. R.; Livi, G. P. Coexpression of human cAMP-specific phosphodiesterase activity and high affinity rolipram binding in yeast. J. Biol. Chem. 1992, 267, 1798-1804. 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.
23. Barnette, M. S.; Manning, C. D.; Cielinski, L. B.; Burman, M.; Christensen, B.; Torphy, T. J. The ability of phosphodiesterase IV inhibitors to suppress superoxide production in guinea pig eosinophils is correlated with inhibition of phosphodiesterase IV catalytic activity. J. Pharmacol. Exp. Ther. 1995, 273, 674-679.
24. Schneider, T.; van Velzen, D.; Moqbel, R.; Issekutz, A. C. Kinetics and quantification of eosinophil and neutrophil recruitment to allergic lung inflammation in a Brown Norway rat model. Am. J. Respir. Cell Mol. Biol. 1997, 17, 702-712. Elwood, W.; Lotvall, J. O.; Barnes, P. J.; Chung, K. F. Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. Allergy Clin. Immunol. 1991, 88, 951-60.
25. Schneider, T.; van Velzen, D.; Moqbel, R.; Issekutz, A. C. Kinetics and quantification of eosinophil and neutrophil recruitment to allergic lung inflammation in a Brown Norway rat model. Am. J. Respir. Cell Mol. Biol. 1997, 17, 702-712. Elwood, W.; Lotvall, J. O.; Barnes, P. J.; Chung, K. F. Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. Allergy Clin. Immunol. 1991, 88, 951-60.
26. Goldie, R. G.; Pedersen, K. E. Mechanisms of increased airway microvascular permeability: role in airway inflammation and obstruction. Clin. Exp. Pharmacol. Physiol. 1995, 22, 387-396.
27. Engels, P.; Sullivan, M.; Müller, T.; Lübbert, H. Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype. FEBS Lett. 1995, 358, 305-310.
28. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.