Synthesis, antifungal activity, and molecular modeling studies of new inverted oxime ethers of oxiconazole

Journal of Medicinal Chemistry

Volumn 45, Issue 22, 2002, Pages 4903-4912

  Rossello, Armando ^a   Bertini, Simone ^a   Lapucci, Annalina ^a   Macchia, Marco ^a   Martinelli, Adriano ^a   Rapposelli, Simona ^a   Herreros, Esperanza ^b   Macchia, Bruno ^a  

^a UNIVERSITY OF PISA   (Italy)

^b GLAXOSMITHKLINE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1 [1 [4 [2 (4 MORPHOLINYL)ETHOXY]PHENYL]ETHYLIDENEAMINOXY] 1 (2,4 DICHLOROPHENYL) 2 (1H IMIDAZOL 1 YL)ETHAN; 1 [1 [4 [2 (4 MORPHOLINYL)ETHOXY]PHENYL]ETHYLIDENEAMINOXY] 1 (2,4 DIFLUOROPHENYL) 2 (1H IMIDAZOL 1 YL)ETHAN; 1 [1 [4 [2 (4 MORPHOLINYL)ETHOXY]PHENYL]METHYLENEAMINOXY] 1 (2,4 DICHLOROPHENYL) 2 (1H IMIDAZOL 1 YL)ETHAN; 1 [1 [4 [2 (4 MORPHOLINYL)ETHOXY]PHENYL]METHYLENEAMINOXY] 1 (2,4 DIFLUOROPHENYL) 2 (1H IMIDAZOL 1 YL)ETHAN; ANTIFUNGAL AGENT; CYTOCHROME P450; CYTOCHROME P450 14ALPHA STEROL DEMETHYLASE; METHYLTRANSFERASE; OXICONAZOLE; OXIME; UNCLASSIFIED DRUG;

ARTICLE; CANDIDA ALBICANS; CONTROLLED STUDY; DILUTION; DRUG STRUCTURE; DRUG SYNTHESIS; FUNGICIDAL ACTIVITY; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR MODEL; NONHUMAN; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANTIFUNGAL AGENTS; ASPERGILLUS FUMIGATUS; CANDIDA; CRYPTOCOCCUS NEOFORMANS; CYTOCHROME P-450 ENZYME SYSTEM; ETHERS; IMIDAZOLES; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; OXIDOREDUCTASES; OXIMES; RECOMBINANT FUSION PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TRICHOPHYTON;

EID: 0037168067     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020980t     Document Type: Article

References (34)

1. Onishi, J.; Meinz, M.; Thompson, J.; Curotto, J.; Dreikorn, S.; Rosenbach, M.; Douglas, C.; Abruzzo, G.; Flattery, A.; Kong, L.; Cabello, A.; Vicente, F.; Pelaez, F.; Diez, M. T.; Martin, I.; Bills, G.; Giacobbe, R.; Dombrowski, A.; Schwartz, R.; Morris, S.; Harris, G.; Tsipouras, A.; Wilson, K.; Kurtz, M. B. Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob. Agents Chemother. 2000, 44, 368-377.
2. Ghannoum, M. A.; Rice, L. B. Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of these Mechanisms with Bacterial Resistance. Clin. Microbiol. Rev. 1999, 12, 501-517.
3. Sheehan, D. J.; Hitchcock, C. A.; Sibley, C. M. Current and Emerging Azole Antifungal Agents. Clin. Microbiol. Rev. 1999, 12, 40-79.
4. Lartey, P. A.; Moehle, C. M. Recent Advances in Antifungal Agents. In Annual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: NY, 1997; Vol. 32, pp 151-169.
5. Balkovec, J. M. Nonazole Antifungal Agents. InAnnual Reports in Medicinal Chemistry; Bristol, J. A., Ed.; Academic Press: NY, 1998; Vol. 33, pp 173-182.
6. Watkins, W. J.; Renau, T. E. Progress with Antifungal Agents and Approaches to Combat Fungal Resistance. In Annual Reports in Medicinal Chemistry; Doherty, A. M., Ed.; Academic Press: NY, 1999; Vol. 35, pp 157-166.
7. Polak, A. Oxiconazole, a new imidazole derivative. Evaluation of antifungal activity in vitro and in vivo. Arzneim. Forsch. 1982, 32, 17-24.
8. Polak, A. Antifungal Activity In Vitro of Ro 14-4767/002, A Phenylpropyl-morpholine. Sabouradia 1983, 21, 205-213.
9. Macchia, B.; Balsamo, A.; Breschi, M. C.; Chiellini, G.; Macchia, M.; Martinelli, A.; Martini, C.; Nardini, C.; Nencetti, S.; Scatizzi, R.; Rossello, A. The [(Methyloxy)imino]methyl moiety as a bioisoster of aryl. A novel class of completely aliphatic β-adrenergic receptor antagonists. J. Med. Chem. 1994, 37, 1518-1525.
10. Macchia, M.; Menchini, E.; Orlandini, E.; Rossello, A.; Broccali, G.; Visconti, M. Synthesis And Antimicrobial Activity Of 7β-[N-(Arylmethyloxyimino)Acetamido]cephalosporanic Acid Derivatives. Farmaco 1995, 50, 713-718.
11. 2-Dopaminergic Binding Affinity. Farmaco 1996, 51, 33-39.
12. Balsamo, A.; Macchia, M.; Martinelli, A.; Rossello, A. The [(Methyloxy)imino]methyl Moiety (MOIMM) In The Design Of A New Type Of β-Adrenergic Blocking Agent. Eur. J. Med. Chem. 1999, 34, 283-291.
13. Vanden Bossche, H. In Sterol Biosynthesis Inhibitors. Pharmaceutical and Agrochemical Aspects; Berg, D., Plembel, M., Eds.; Ellis Horwood: Chichester, England, 1988; pp 79-119.
14. Wermuth, C. G. Specific Substituent effects. In The Practice of Medicinal Chemistry; Wermuth, C. G., Ed.; Academic Press Inc.: San Diego, CA, 1996; pp 311-344.
15. Cooper, P.; Wright, J. J.; Ganguly, A. K.; Desai, J.; Loebenberg, D.; Parmegiani, R.; Feingold, D. S.; Sud, I. J. Synthesis of 14-α-Aminomethyl Substituted Lanosterol Derivative; Inhibitors of Fungal Ergosterol Biosynthesis. J. Chem. Soc. Chem. Commun. 1989, 898-900.
16. Troke, P. F.; Andrews, J. R.; Pye, G. W.; Richardson, K. Fluconazole and other Azoles: Translation of In Vivo and Clinical Efficacy. Rev. Infect. Dis. 1990, 12, 276-280.
17. Gebhart, R. J.; Espinel-Ingroff, A.; Shadomy, S. In Vitro Susceptibility Studies with Oxiconazole (Ro 13-8996). Chemotherapy 1984, 30, 244-247.
18. Rotstein, D. M.; Kertesz, D. J.; Walker, K. M.; Swinney, D. C. Stereoisomers of ketoconazole: preparation and biological activity. J. Med. Chem. 1992, 35, 2818-2825.
19. Sharpe, C. J.; Shadbolt, R. S.; Ashford, A.; Ross, J. W.; Phenacylthioimidazolines and 3-aryl-5,6-dihydroimidazo(2,1-b)thiazoles with antidepressant activity. J. Med. Chem. 1971, 14, 977-982.
20. Godefroy, E. F.; Heeres, J.; Cutsem, J. The Preparation and Antimycotic Properties of Derivatives of 1-Phenethylimidazole. J. Med. Chem. 1969, 12, 784-791.
21. Sheehan, J. T. Synthesis of 2,4-Dichloropropiophenone. Am. Chem. Soc. 1946, 68, 1672.
22. Ogata, M.; Matsumoto, H.; Takahashi, K.; Shimizu, S.; Kida, S. Synthesis and oral antifungal activity of novel azolylpropanolones and related compounds. J. Med. Chem. 1987, 30, 1054-1068.
23. Ramirez, M.; Garey, D.; Pena, M. An Approach to Substituted 4-Hydroxy-pyran-2-ones. J. Heterocycl. Chem. 1995, 32, 1657- 1660.
24. Macchia, B.; Gentili, D.; Macchia, M.; Mamone, F.; Martinelli, A.; Orlandini, E.; Rossello, A.; Cercignani, G.; Pierotti, R.; Allegretti, M.; Asti, C.; Caselli, G. Synthesis, Inhibitory Activity Towards Human Leukocyte Elastase and Molecular Modeling Studies of 1-carbamoyl-4-methyleneaminoxyazetidinones. Eur. J. Med. Chem. 2000, 35, 53 -67.
25. Liao, Y. W.; Li, H. X. Enantioselective synthesis and antifungal activity of optically active econazole and miconazole. Yao Xue Xue Bao 1993, 28, 22-27.
26. The MFC is the lowest concentration of an antimicrobial agent that causes at least a 3-log10 reduction in the number of surviving cells (as compared with the initial preincubation concentration). A drug is considered fungicidal when the difference between the MIC and the MFC is lower than three double dilutions
27. Podust, L. M.; Poulos, T. L.; Waterman, M. R. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium Tubercolosis in complex with azole inhibitors. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 3068-3073.
28. Podust, L. M.; Stojan, J.; Poulos, T. L.; Waterman, M. R. Substrate recognition sites in 14α-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. J. Inorg. Biochem. 2001, 87, 227-235.
29. Ji, H.; Zhang, W.; Zhou, Y.; Zhang, M.; Zhu, J.; Song, Y.; Lü, J.; Zhu, J. A Three-Dimensional Model of Lanosterol 14-Demethylase of Candida albicans and Its Interaction with Azole Antifungals. J. Med. Chem. 2000, 43, 2493-2505.
30. NCCLS. 1997. Reference Method for Broth Dilution Antifungal Susceptibility testing of Yeasts. Approved Standard. NCCLS document M27-A.
31. NCCLS. 1998. Reference Method for Broth Dilution Antifungal Susceptibility testing of Conidium-Forming Filamentous Fungi; Proposed Standard. NCCLS document M38-P.
32. Discover, version 2.9.5; Biosym Technologies, San Diego, CA.
33. Modeling a heme protein with CVFF. http//www.accelrys.com/support/life/discover/forcefield/cvffCYT.html.
34. Thompson, J. D.; Higgings, D. G.; Gibson, T. J.; Clustar, W. Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22, 4673-4680.