Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders: Structure-Activity Relationship

Journal of Medicinal Chemistry

Volumn 47, Issue 8, 2004, Pages 2075-2088

  Jönsson, Stig ^a   Andersson, Gunnar ^a   Fex, Tomas ^a,b   Fristedt, Tomas ^a   Hedlund, Gunnar ^a   Jansson, Karl ^a   Abramo, Lisbeth ^a   Fritzson, Ingela ^a   Pekarski, Olga ^a   Runström, Anna ^a   Sandin, Helena ^a   Thuvesson, Ingela ^a   Björk, Anders ^a  

^a Active Biotech Research AB   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

1,2 DIHYDRO 4 HYDROXY 2 OXO 3 QUINOLINECARBOXAMIDE DERIVATIVE; LAQUINIMOD; QUINOLINE DERIVATIVE; ROQUINIMEX; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL MODEL; ARTICLE; AUTOIMMUNE DISEASE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DOG; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; FEVER; INHIBITION KINETICS; MOUSE; NEUTROPHILIA; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; AUTOIMMUNE DISEASES; DOGS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; HYDROXYQUINOLINES; MICE; MICE, INBRED C57BL; QUINOLONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 11144357311     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm031044w     Document Type: Article

References (23)

1. Whitaker, J. N.; Mitchell, G. W. Experimental Allergic Encephalomyelitis as a Guide to the Understanding of Treatment of Multiple Sclerosis. Ann. Neurol. 1993, 34, 636-637.
2. Taylor, R. S. Immunologic Aspects of Multiple Sclerosis. Phys. Med. Rehabil. Clin. N. Am. 1998, 9, 525-536.
3. Karussis, D. M.; Lehmann, D.; Slavin, S.; Vourka-Karussis, U.; Mizrachi-Koll, R.; Ovadia, H.; Ben-Nun, A.; Kalland, T.; Abramsky, D. Inhibition of Acute, Experimental Autoimmune Encephalomyelitis by the Synthetic Immunomodulator Linomide. Ann. Neurol. 1993, 34, 654-660.
4. Karussis, D. M.; Lehmann, D.; Slavin, S.; Vourka-Karussis, U.; Mizrachi-Koll, R.; Ovadia, H.; Kalland, T.; Abramsky, O. Treatment of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis with the Synthetic Immunomodulator Linomide (Quinoline-3-carboxamide). Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6400-6404.
5. Pekarski, O.; Björk, J.; Hedlund, G.; Andersson, G. The Inhibitory Effect in Experimental Autoimmune Encephalomyelitis by the Immunomodulatory Drug Linomide (PNU-212616) Is Not Mediated via Release of Endogenous Glucocorticoids. Autoimmunity 1998, 28, 235-241.
6. Brunmark, C.; Runström, A.; Ohlsson, L.; Sparre, B.; Brodin, T.; Åström, M.; Hedlund, G. The New Orally Active Immuno-regulator Laquinimod (ABR-215062) Effectively Inhibits Development and Relapses of Experimental Autoimmune Encephalomyelitis. J. Neuroimmunol. 2002, 130, 163-172.
7. Diab, A.; Michael, L.; Wahren, B.; Deng, G. M.; Björk, J.; Hedlund, G.; Zhu, J. Linomide Suppresses Acute Experimental Autoimmune Encephalomyelitis in the Lewis Rats by Counteracting the Imbalance of Pro-inflammatory versus Anti-inflammatory Cytokines. J. Neuroimmunol. 1998, 85, 146-154.
8. Tian, W.-Z.; Navikas, V.; Matusevicius, D.; Söderström, M.; Fredrikson, S.; Hedlund, G.; Link, H. Linomide (roquinimex) Affects the Balance between Pro- and Anti-inflammatory Cytokines in Vitro in Multiple Sclerosis. Acta Neurol. Scand. 1998, 98, 94-101.
9. Noseworthy, J. H.; Wolinsky, J. S.; Lublin, F. D.; Whitaker, J. N.; Linde, A.; Gjorstrup, P.; Sullivan, H. C. Linomide in Relapsing and Secondary Progressive MS: Part I: Trial Design and Clinical Results. North American Linomide Investigators. Neurology 2000, 54, 1726-1733.
10. Wolinsky, J. S.; Narayana, P. A.; Noseworthy, J. H.; Lublin, F. D.; Whitaker, J. N.; Linde, A.; Gjorstrup, P.; Sullivan, H. C. Linomide in Relapsing and Secondary Progressive MS: Part II: MRI Results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide investigators. Neurology 2000, 54, 1734-1741.
11. Corall, R. A.; Orazi, O. O.; Autino, J. C. Total Synthesis of Phenolic Balfourodendron Alkaloids. Tetrahedron Lett. 1983, 24, 2359-2360.
12. Coppola, G. M. The Chemistry of Isatoic Anhydride. Synthesis 1980, 505-536.
13. Coppola, G. M.; Hardtmann, G. E.; Pfister, O. R. Chemistry of 2H-3,1-Benzoxazine-2,4(1H)dione (Isatoic Anhydride). 2. Reactions with Thiopseudoureas and Carbanions. J. Org. Chem. 1976, 41, 825-831.
14. Krantz, A.; Young, J. M. Novel Use for Carbamoyl Benzoates. U.S. Patent No. 4,873,232, Oct. 10, 1989.
15. Klaubert, D. H.; Sellstedt, J. H.; Guinosso, C. J.; Capetola, R. J.; Bell, S. C. N-(Aminophenyl) Oxamic Acids and Esters as Potent, Orally Active Antiallergy Agents. J. Med. Chem. 1981, 24, 742-748.
16. Hewawasam, P.; Meanwell, N. A General Method for the Synthesis of Isatins: Preparation of Regiospecifically Functionalized Isatins from Anilines. Tetrahedron Lett. 1994, 35, 7303-7306.
17. Hynes, J. B.; Pathak, A.; Panos, C. H.; Okeke, C. C. Direct Synthesis of 2,4-Diaminoquinazolines from 2-Fluorobenzonitriles. J. Heterocycl. Chem. 1988, 25, 1173-1177.
18. Björk, A.; Jönsson, S.; Fex, T.; Hedlund, G. Quinoline Derivatives. U.S. Patent No. 6,077,851, June 20, 2000.
19. Johnstone, R. A. W.; Payling, D. W.; Thomas, C. A Rapid Method of N-Alkylating of Amines. J. Chem. Soc. 1969, 2223-2224.
20. Alluni, S.; Clementi, S.; Edlund, U.; Johnels, D.; Hellberg, S.; Sjöström, M.; Wold, S. Multivariate Data Analysis of Substituent Descriptors. Acta Chem. Scand. B 1983, 37, 47-53.
21. For a review or discussion on these properties, see the following. Kubinyi, H. Parameters. In Methods and Principles in Medicinal Chemistry. QSAR: Hansch Analysis and Related Approaches; Mannhold, R., Kroogsgard-Larsen, P., Timmermann, H., Eds.; VCH: Weinheim, Germany,1993; Vol. 1, Chapter 3, pp 21-36.
22. Tsuji, K.; Spears, G. W.; Nakamura, K.; Tojo, T.; Seki, N.; Sugiyama, S. ; Matsuo, M. Synthesis and Antinephritic Activities of Quinoline-3-carboxamidesand Related Compounds. Bioorg. Med. Chem. Lett. 2002, 12, 85-88.
23. Zou, L.-P.; Abbas, N.; Volkmann, I.; Nennesmo, I.; Levi, M.; Wahren, B.; Winblad, B.; Hedlund, G.; Zhu, J. Suppression of experimental autoimmine neuritis by ABR-215062 is associated with altered Th1/th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue. Neuropharmacology 2002, 42, 731-739.