2-amino-3-substituted-6-[(E)-1-phenyl-2-(N- methylcarbamoyl)vinyl]imidazo-[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: Stereospecific synthesis and antiviral activity

Journal of Medicinal Chemistry

Volumn 42, Issue 1, 1999, Pages 50-59

  Hamdouchi, Chafiq ^a   De Blas, Jesús ^a   Del Prado, Mirian ^a   Gruber, Joseph ^b   Heinz, Beverly A ^b   Vance, Lori ^b  

^a ELI LILLY AND COMPANY   (Spain)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 (2 TRIFLUOROMETHYL 4 FLUOROPHENYL) 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; 2 AMINO 3 (2,3,4 TRIFLUOROPHENYL) 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; 2 AMINO 3 (2,5 DIFLUOROPHENYL) 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; 2 AMINO 3 (TRIFLUOROMETHYLPHENYL) 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; 2 AMINO 3 PHENYL 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; 2 AMINO 6 [1 PHENYL 2 (N METHYLCARBAMOYL)VINYL]IMIDAZO[1,2 A]PYRIDINE; AMIDE; BENZIMIDAZOLE DERIVATIVE; ENVIROXIME; HALOGEN; METAL; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN RHINOVIRUS; ISOMER; NUCLEAR OVERHAUSER EFFECT; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION;

EID: 0033552891     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9810405     Document Type: Article

References (27)

1. (a) Couch, R. B. Rhinoviruses. In Virolgy; Fields, B. N., Ed.; Raven Press: New York, 1990; Chapter 22, pp 607-629.
2. (b) Rueckert, R. R. Picornaviruses and their Replication. In Virolgy; Fields, B. N., Ed.; Raven Press: New York, 1985; Chapter 32, pp 705-738.
3. (c) Monto, A. S.; Bryan, E. R. Ohmit, S. Rhinovirus Infections in Tecumseh, Michigan: Frequency of Illness and Number of Serotypes. J. Infect. Dis. 1987, 154, 43-49.
4. (d) Blaas, D.; Hofer, F.; Gruenberger, M.; Kowalski, H.; Machact, H.; Kuechler, E.; Huettinger, M. Entry of Minor Group Human Rhinoviruses into the Cell. Cellular Receptor for Animal Viruses; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 1994; pp 129-140.
5. (e) Chapman, M. S.; Rossmann, M. G. Comparison of the Surface Properties of Picornaviruses. Virology 1993, 195, 745-756.
6. (a) Wikel, J. H.; Paget, C. J.; DeLong, D. C.; Nelson, J. D.; Wu, C. Y. E.; Paschal, J. W.; Dinner, A.; Templeton, R. J.; Chaney, M. O.; Jones, N. D.; Chamberlin, J. W. Synthesis of Syn and Anti Isomers of 6-[[(Hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2- amine. Inhibitors of Rhinovirus Multiplication. J. Med. Chem. 1980, 23, 368-372.
7. (b) DeLong, D. C. Effect of Enviroxime on Rhinovirus Infections in Humans. In Microbiology; Leive, L., Schlessinger, D., Eds.; American Society for Microbiology: Washington, DC, 1984; pp 431-434.
8. (c) DeLong, D. C.; Reed, S. E. Inhibition of Rhinovirus Replication in Organ Culture by a Potential Antiviral Drug. J. Infect. Dis. 1980, 141, 87-91.
9. (a) Victor, F.; Loncharich, R.; Tang, J.; Spitzer, A. W. Synthesis and Antiviral Activity of C2 Analogues of Enviroxime: An Exploration of the Role of Critical Functionality. J. Med. Chem. 1997, 40, 3478-3483.
10. (b) Victor, F.; Brown, T. J.; Campanale, K.; Heinz, B. A.; Shipley, L. A.; Su, K. S.; Tang, J.; Vance, L. M.; Spitzer, W. A. Synthesis, Antiviral Activity, and Biological Properties of Vinylacetylene Analogues of Enviroxime. J. Med. Chem. 1997, 40, 1511-1518.
11. Heinz, B. A.; Vance, L. M. The Antiviral Compound Enviroxime Targets the 3A Coding Region of Rhinovirus and Poliovirus. J. Virol. 1995, 69, 4189-4197.
12. (b) Heinz, B. A.; Vance, L. M. Sequence Determinants of 3A-Mediated Resistance to Enviroxime in Rhinoviruses and Enteroviruses. J. Virol. 1996, 70, 4854-4857.
13. (a) Phillpotts, R. J.; DeLong, D. C.; Wallace, J.; Jones, R. W.; Reed, S. E.; Tyrrell, D. A. Rhinovirus Infection in Man. Lancet 1981, 1/8234, 1342-1344.
14. (b) Miller, F. D.; Monto, A. S.; DeLong, D. C.; Exelby, A.; Bryan, E. R.; Srivastava, S. Controlled Trial of Enviroxime Against Natural Rhinovirus Infections in a Community. Antimicrob. Agents Chemother. 1985, 27, 102-106.
15. (a) Enviradene (IND 20204); Virology Section, Summary; p 58, unpublished results.
16. (b) Enviradene (IND 20204); IND Protocol No. 3; pp 1457-1461, unpublished results.
17. Tebbe, M. J.; Spitzer, W. A.; Victor, F.; Miller, S. C.; Lee, C. C.; Sattelberg, T. R.; McKinney, E., Sr.; Tang, J. C. Antirhino/ Enteroviral Vinyl Acetylene Benzimidazoles: A Study of Their Activity and Oral Plasma Levels in Mice. J. Med. Chem. 1997, 40, 3937-3946.
18. Kelley, J. L.; McLean, W.; Ronda, G. D.; Crouch, R. Synthesis of 6-[[(Hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-imidazo[4,5-b] pyridin-2-amine. An Aza Analogue of Enviroxime. J. Heterocycl. Chem. 1990, 27, 1821.
19. Ogata, M.; Matsumoto, H.; Shimizu, S.; Kida, S.; Wada, T.; Shiro, M.; Sato, K. Synthesis and Antiviral activity of Sulfonamido-benzophenon Oximes and Sulfonamidobenzamides. J. Med. Chem. 1986, 29, 417-423.
20. (a) Bochis, R. J.; Olen, L. E.; Fisher, M. H.; Reamer, R. A.; Wilks, G.; Taylor, J. E.; Olson, G. Isomeric Phenylthioimidazo[1,2-a]-pyridines as Anthelmintics. J. Med. Chem. 1981, 24, 1483.
21. (b) Montgomery, J. A. Secrist, A. A. In Comprehensive Heterocycle Chemistry; Katritzky, A. R., Ed.; Pergamon Press: Oxford, 1984; Chapter 4.10, p 607 and references therein.
22. (c) Gueiffer, A.; Viols, H.; Blache, Y.; Chavignon, O.; Teulade, J. C.; Aumelas, A.; Chapat, J. P. Heterocycles 1994, 38, 55.
23. Hay, L. A.; Mitchell, D. A. Regio and Stereocontrolled Method for Preparing 3,3-Diarylacrylamides. Tetrahedron Lett. 1997, 38, 6533-6536.
24. Attempts of N-detrifluoroacetylation of compound 7a using Hünig's base failed to yield the desired amine. Instead the reaction led to imidazo ring opening providing the aminopyridine as the main product.
25. Tang, J.; Colacino, J. M.; Larsen, S. H.; Spitzer, W. Virucidal Activity of Hypericin Against Enveloped and Nonenveloped DNA and RNA Viruses. Antiviral Res. 1990, 13, 313-326.
26. Scudiero, D. A.; Shoemaker, R. H.; Paull, K. D.; Monk, A.; Tierney, S.; Notziger, T. H.; Currens, M. J.; Seniff, D.; Boyd, M. R. Evaluation of a Soluble Tetrazolium/Formazan Assay for Cell Growth and Drug Sensitivity in Culture Using Human and Other Tumor Cell Lines. Cancer Res. 1988, 48, 4827-4833.
27. Reed, L. J.; Muench, H. A. A Simple Method of Estimating Fifty Percent Endpoints. J. Am. Hyg. 1938, 27, 493-497.