Synthesis and structure - Activity-relationships of 1H-imidazo[4,5-c] quinolines that induce interferon production

Journal of Medicinal Chemistry

Volumn 48, Issue 10, 2005, Pages 3481-3491

  Gerster, John F ^a   Lindstrom, Kyle J ^a   Miller, Richard L ^a   Tomai, Mark A ^a   Birmachu, Woubalem ^a   Bomersine, Shannon N ^a   Gibson, Shiela J ^a   Imbertson, Linda M ^a   Jacobson, Joel R ^a   Knafla, Roy T ^a   Maye, Peter V ^a   Nikolaides, Nickolas ^a   Oneyemi, Folakemi Y ^a   Parkhurst, Gwen J ^a   Pecore, Sharon E ^a   Reiter, Michael J ^a   Scribner, Lisa S ^a   Testerman, Tracy L ^a   Thompson, Natalie J ^a   Wagner, Tammy L ^a   Weeks, Charles E ^a   Andre, Jean Denis ^a   Lagain, Daniel ^a   Bastard, Yvon ^a   Lupu, Michel ^a   more..

^a 3M COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 METHYLPROPYL) 1H IMIDAZO[4,5 C]QUINOLIN 4 AMINE; 1 (2 METHYLPROPYL) 2 PHENOXYMETHYL 1H IMIDAZO[4,5 C]QUINOLIN 4 AMINE; IMIQUIMOD; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ACTINIC KERATOSIS; ANTIVIRAL ACTIVITY; ARTICLE; BASAL CELL CARCINOMA; CELL CULTURE; CONDYLOMA; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG APPROVAL; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; GUINEA PIG; HERPES SIMPLEX VIRUS 2; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTERFERON INDUCTION; INTERFERON PRODUCTION; PERIPHERAL BLOOD MONONUCLEAR CELL; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; VIRUS INHIBITION;

AMINOQUINOLINES; ANIMALS; ANTIVIRAL AGENTS; CELL LINE, TUMOR; CELLS, CULTURED; CYTOPATHOGENIC EFFECT, VIRAL; GUINEA PIGS; HERPESVIRUS 2, HUMAN; HUMANS; IMIDAZOLES; INTERFERON INDUCERS; INTERFERONS; LEUKOCYTES, MONONUCLEAR; QUINOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 20844452063     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049211v     Document Type: Article

References (26)

1. Isaacs, A.; Lindenmann, J. Virus Interference. I: The Interferon. Proc. R. Soc., Ser. B 1957, 147, 258-267.
2. Weirenga, W. Interferon Inducers. Annu. Rep. Med. Chem. 1982, 18, 151-161.
3. (a) Tomai, M. A.; Birmachu, W.; Case, M. T.; Gerster, J. F.; Gibson, S. J.; Imbertson, L. M.; Miller, R. L.; Reiter, M. J.; Wagner, T. L. Imiquimod: In Vivo and in Vitro Characteristics and Toxicology. In Cutaneous Infection and Therapy; Aly, R., Beutner, K. R., Maibach, H., Eds.; Marcel Dekker: New York, 1997; Chapter 32.
4. (b) Miller, R. L.; Gerster, J. F.; Owens, M. L.; Slade, H. B.; Tomai, M. A. Imiquimod applied topically: a novel immune response modifier and a new class of drug. Int. J. Immunopharmacol. 1999, 21, 1-14.
5. Arany, I.; Tyring, S. K.; Stanley, M. A.; Tomai, M. A.; Miller, R. L.; Smith, M. H.; McDermott, D. J.; Slade, H. B. Enhancement of the Innate and Cellular Immune Response in Patients with Genital Warts Treated with Topical Imiquimod Cream 5%. Antiviral Res. 1999, 43, 53-63.
6. De Clercq, E.; Descamps, J.; De Somer, P. (S)-9-(2,3-Dihydroxypropyl) adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity. Science 1978, 200, 563-565.
7. Miller, R. L.; Imbertson, L. M.; Reiter, M. J.; Gerster, J. F. Treatment of Primary Herpes Simplex Virus Infection in Guinea Pigs by Imiquimod. Antiviral Res. 1999, 44, 31-42.
8. Weeks, C. E.; Gibson, S. J. Induction of Interferon and Other Cytokines by Imiquimod and Its Hydroxylated Metabolite R-842 in Human Blood Cells in Vitro. J. Interferon Res. 1994, 14, 81-85.
9. Gabriel, S. Zur Kenntnis einiger Chinolin-Abkömmlinge (Information about Some Quinoline Derivatives). Chem. Ber. 1918, 51, 1506-1515.
10. Izumi, T.; Sakaguchi, J.; Takeshita, M.; Tawara, H.; Kato, K.-I.; Dose, H.; Tsujino, T.; Watanabe, Y.; Kato, H. 1H-Imidazo[4,5-c]quinoline Derivatives as Novel Potent TNF-α Suppressors: Synthesis and Structure - Activity Relationship of 1-, 2-and 4-Substituted 1H-Imidazo[4,5-c]quinolines or 1H-Imidazo[4,5-c]pyridines. Bioorg. Med. Chem. 2003, 11, 2541-2550.
11. Hamana, M.; Hoshino, O. Studies on Tertiary Amine Oxides. XXII. Reactions of Quinoline 1-Oxide with Amines in the Presence of Acylating Agents. Yakugaku Zasshi 1964, 84, 35-41.
12. 1H NMR analysis using a combination of NMR experiments (proton, carbon, gHMQC, and gHMBC). The long-range C-H correlations from the gHMBC experiment along with the proton coupling constants of the aromatic peaks are consistent with the assigned structure.
13. Chen, L.-Z.; Liu, X.; Ridgewell, R. E. Identification of R-837 Metabolites in the Presence of Human Liver Microsomes. Presented at the Annual Meeting of the American Association of Pharmaceutical Scientists (AAPS), New Orleans, LA, November 1999.
14. (a) Slade, H. B.; Owens, M. L.; Tomai, M. A.; Miller, R. L. Imiquimod 5% Cream (Aldara). Expert Opin. Invest. Drugs 1998, 7 (3), 437-449.
15. (b) Edwards, L.; Ferenczy, A.; Eron, L.; Baker, D.; Owens, M. L.; Fox, T. L.; Hougham, A. J.; Schmitt, K. A; HPV Study Group. Self Administrated Topical 5% Imiquimod Cream for External Anogenital Warts. Arch. Dermatol. 1998, 134, 25-30.
16. (a) Marks, R.; Gebauer, K.; Shumack, S.; Amies, M.; Bryden, J.; Fox, T. L.; Owens, M. L. Imiquimod 5% Cream in the Treatment of Superficial Basal Cell Carcinoma: Results of a Multicenter 6-Week Dose-Response Trial. J. Am. Acad. Dermatol. 2001, 44, 807-813.
17. (b) Geisse, J.; Caro, I.; Lindholm, J.; Golitz, L.; Stampone, P.; Owens, M. Imiquimod 5% Cream for the Treatment of Superficial Basal Cell Carcinoma: Results from Two Phase III, Randomized, Vehicle-Controlled Studies. J. Am. Acad. Dermatol. 2004, 50, 722-733.
18. (a) Stockfleth, E.; Meyer, T.; Benninghoff, B.; Salasche, S.; Papadopoulos, L.; Ulrich, C.; Christophers, E. A Randomized, Double-Blind, Vehicle-Controlled Study To Assess 5% Imiquimod Cream for the Treatment of Multiple Actinic Keratoses. Arch. Dermotol. 2002, 138, 1498-1502.
19. (b) Lebwohl, M.; Dinehart, S.; Whiting, D.; Lee, P. K.; Tawfik, N.; Jorizzo, J.; Lee, J. H.; Fox, T. L. Imiquimod 5% cream for the treatment of actinic keratosis: Results form two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J. Am. Acad. Dermatol. 2004, 50, 714-721.
20. (a) Salasche, S., Shumak, S., Eds. Clinical Experience with the Immune Response Modifier Imiquimod for the Treatment of Dermatological Conditions: Case Series. In Clinical and Experimental Dermatology; Blackwell Scientific Publications: Oxford, 2003; Vol. 28 (Suppl. 1).
21. (b) Christophers, E., Rigel, D., Eds. The Therapeutic Potential of Immune Response Modifiers in Dermatology: Case Series. In British Journal of Dermatology; Blackwell Scientific Publications: Oxford, 2003; Vol. 149 (Suppl. 66).
22. Recently, some 8-hydroxyadenine derivatives have been described that have similar IFN inducing properties in mouse spleen cells: (a) Hirota, K.; Kazaoka, K.; Niimoto, I.; Kumihara, H.; Sajiki, H.; Isobe, Y.; Takaku, H.; Tobe, M.; Ogita, H.; Ogino, T.; Ichii, S.; Kurimoto, A.; Kawakami, H. Discovery of 8-Hydroxyadenines as a Novel Type of Interferon Inducer. J. Med. Chem. 2002, 45, 5419-5422.
23. (b) Kurimoto, A.; Ogino, T.; Ichii, S.; Isobe, Y.; Tobe, M.; Ogita, H.; Takaku, H.; Sajiki, H.; Hirota, K.; Kawakami, H. Synthesis and Evaluation of 2-Substituted 8-Hydroxyadenines as Potent Interferon Inducers with Improved Oral Bioavailabilities. Bioorg. Med. Chem. 2004, 12, 1091-1099.
24. Buckle, D. R.; Cantello, B. C. C.; Smith, H.; Spicer, B. A. 4-Hydroxy-3-nitro-2-quinolones and Related Compounds as Inhibitors of Allergic Reactions. J. Med. Chem. 1975, 18, 726-732.
25. Compound 28 was also prepared in the following paper: Yoshioka, H.; Matsuya, Y.; Choshi, T.; Sugino, E.; Hibino, S. Synthesis of the Interferon-α Inducer Imiquimod by Thermal Electrocyclic Reactions of 1- and 2-Azahexatriene Systems. Chem. Pharm. Bull. 1996, 44, 709-714.
26. Compound 41 was also prepared in the following paper: van Galen, P. J. M.; Nissen, P.; van Wijngaarden, I.; Ijzerman, A. P.; Soudijn, W. 1H-Imidazo[4,5-c]quinoline-4-amines: Novel Non-Xanthine Adenosine Antagonists. J. Med. Chem. 1991, 34, 1202-1206.