Synthesis and antibacterial activity of novel C12 vinyl ketolides

Journal of Medicinal Chemistry

Volumn 49, Issue 5, 2006, Pages 1730-1743

  Burger, Matthew T ^a   Lin, Xiaodong ^a   Chu, Daniel T ^a   Hiebert, Christy ^a   Rico, Alice C ^a   Seid, Mehran ^a   Carroll, Georgia L ^a   Barker, Lynn ^a   Huh, Kay ^a   Langhorne, Mike ^a   Shawar, Ribhi ^a   Kidney, Jolene ^a   Young, Kelly ^a   Anderson, Scott ^a   Desai, Manoj C ^a   Plattner, Jacob J ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; CLARITHROMYCIN; ERYTHROMYCIN DERIVATIVE; KETOLIDE; MACROLIDE; METHYL GROUP; TELITHROMYCIN; VINYL DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG HALF LIFE; DRUG POTENCY; DRUG SYNTHESIS; HAEMOPHILUS INFLUENZAE; LUNG INFECTION; MALE; NONHUMAN; PHARMACODYNAMICS; RAT; STREPTOCOCCUS PNEUMONIAE;

ANIMALS; ANTI-BACTERIAL AGENTS; BIOLOGICAL AVAILABILITY; DRUG RESISTANCE, BACTERIAL; ENTEROCOCCUS FAECALIS; HAEMOPHILUS INFECTIONS; HAEMOPHILUS INFLUENZAE; HALF-LIFE; KETOLIDES; LUNG DISEASES; MALE; MICROBIAL SENSITIVITY TESTS; PNEUMOCOCCAL INFECTIONS; RATS; RATS, SPRAGUE-DAWLEY; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; STREPTOCOCCUS PYOGENES; STRUCTURE-ACTIVITY RELATIONSHIP; VINYL COMPOUNDS;

EID: 33644871503     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm051157a     Document Type: Article

References (45)

1. (a) Macrolides: Chemistry, Pharmacology and Clinical Uses: Bryskier, A. J., Butzler, J.-P., Neu, H. C., Tulkens, P. M., Eds.; Arnette Blackwell: Paris, 1993.
2. (b) New Macrolides, Azalides, and Streptogramins in Clinical Practice; Neu, H. C., Young, L. S., Zinner. S. H., Acar, J. F., Eds.; Marcel Dekker: New York, 1995.
3. (c) Kurath, P.; Jones, P. H.; Egan, R. S.; Perun, T. J. Acid Degradation of Erythromycin A and Erythromycin B. Experientia 1971, 27, 362.
4. (d) Krowicki, K.; Zamojski, A. Chemical Modifications of Erythromycins I. 8,9-Anhydro-6,9-hemiketal of Erythromycin A. J. Antibiot. 1974, 26, 569-574.
5. ( 2) Morimoto, S.; Takahashi, Y.; Watanabe, Y.; Omura, S. Chemical Modification of Erythromycin I. Synthesis and Antibacterial Activity of 6-O-Methylerythroycin A. J. Antibiotics 1984, 37, 343-345.
6. (a) Bright, G.; Nage, A.; Bordner, J.; Desai, K.; Dibrino, J.; Nowakowska, J.; Vincent, L.; Watrous, R.; Sciavolino, F.; English, A.; Retsema, J.; Anderson, M.; Brennan, L.; Borovoy, R.; Cimchowsji, C.; Faiella, J.; Girard, A.; Girard, D.; Herbert, C.; Manousos, M.; Mason, R. Synthesis, in vitro and in vivo activity of novel 9-deoxy-9a-aza-9a-homoerthyromycin A derivatives: a new class of macrolide antibiotics, the azalides. J. Antibiot. 1988, 41, 1029-1047.
7. (b) Retsema, J. A.; Girard, A. E.; Schekly, W.; Manousos, M.; Anderson, M. R.; Bright, G. M.; Borovoy, R. J.; Brennan, L. A.; Mason, R. Spectrum and Mode of Action of Azithromycin (CP-62,-993), a New 15 Membered-Ring Macrolide with Improved Potency against Gram Negative Organisms. Antimicrob. Agents Chemother. 1987, 31, 1939-1947.
8. (a) Chantot, J.-F.; Bryskier, A.; Gase, J.-C. Antibacterial Activity of Roxithromycin: A Laboratory Evaluation. J. Antibiot. 1986, 39, 660-668.
9. (b) Gasc, J. C.; Gouin d'Ambrières, S.; Lutz, A.; Chantot, J. F. New Ether Oxime of Erythromycin A a Structure Activity Relationship Study. J. Antibiot. 1991, 44, 313-330.
10. (a) Leclereq, Q.; Courvalin, P. Bacterial Resistance to Macrolide, Lincosamide and Streptogramin Antibiotics by Target Modification. Antimicrob. Agents Chemother. 1991, 35, 1267-1272.
11. (b) Leclercq, Q.; Courvalin. P. Intrinsic and Unusual Resistance to Macrolide, Lincosamide and Streptogramim Antibiotics in Bacteria. Antimicrob. Agents Chemother. 1991, 35, 1273-1276.
12. ( c) Sutcliffe, J.; Tait-Kamradt, A.; Wondrack, L. Streptococcus pneumoniae and Streptococcus pyogenes Resistant to Macrolides but Sensitive to Clindamycin: A Common Resistance Pattern Mediated by an Efflux System. Antimicrob. Agents Chemother. 1996, 40, 1817-1824.
13. (a) Agouridas, C.; Denis, A.; Auger, J. M.; Benedetti, Y.; Bonnefoy, A.; Bretin, F.; Chantot, J. F.; Dussarat, A.; Fromentin, C.; D'Ambrières, S. G.; Lachaud, S.; Laurin, P.; Le Martret, O.; Loyau, V.; Tessot, N. Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives): A New Class of Antibacterials Highly Potent against Macrolide-Resistant and -Susceptible Respiratory Pathogens. J. Med. Chem. 1998, 41, 4080-4100.
14. ( b) Denis, A.; Agouridas, C.; Auger, J.-M.; Benedetti, Y.; Bonnefoy, A.; Bretin, F.; Chantot, J.-F.; Dussarat, A.; Fromentin, C.; D'Ambrieres, S. G.; Lachaud, S.; Laurin, P.; Martret, O. L.; Loyau, V.; Tessot, N.; Pejac, J.-M.; Perron, S. Synthesis and Antibacterial Activity of HMR 3647. A New Ketolide Highly Potent against Erythromycin-Resistant and Susceptible Pathogens. Bioorg. Med. Chem. Lett. 1999, 9, 3075-3080.
15. Ma, Z.; Clark, R. F.; Brazzale, A.; Wang, S.; Rupp, M. J.; Li, L.; Griesgraber, G.; Zhang, S.; Yong, H.; Phan, L. T.; Nemoto, P. A.; Chu, D. T.; Plattner, J. J.; Zhang, X.; Zhong, P.; Cao, Z.; Nilius, A. M.; Shortridge, V. D.; Flamm, R.; Mitten, M.; Meulbroek, J.; Ewing, P.; Alder, J.; Or, Y. S. Novel Erythromycin Derivatives with Aryl Groups Tethered to the C-6 Position Are Potent Protein Synthesis Inhibitors and Active against Multidrug-Resistant Respiratory Pathogens. J. Med. Chem. 2001, 44, 4137-4156.
16. (a) Harris, D. R.; McGeachin, S. G.; Mills, H. H. The Structure and Stereochemistry of Erythromycin A. Tetrahedron Lett. 1965, 679-685.
17. (b) Awan, A.; Brennan, R. J.; Regan, A. C.; Barber, J. Conformational Analysis of the Erythromycin Analogues Azithromycin and Clarithromycin in Aqueous Solution and Bound to Bacterial Ribosomes. J. Chem. Soc., Chem. Commun. 1995, 1653-1654.
18. (c) Bertho, G.; Ladam, P.; Gharbi-Benarous, J.; Delaforge, M.; Girault, J.-P. Solution Conformation of Methylated Macrolide Antibiotics Roxithromycin and Erythromycin Using NMR and Molecular Modeling. Ribosome-Bound Conformation Determined by TRNOE and Formation of Cytochrome P450-Metabolite Complex. Int. J. Biol. Macromol. 1998, 22, 103-127.
19. ( d) Bertho, G.; Gharbi-Benarous, J.; Delaforge, M.; Girault, J.-P. Transferred Nuclear Overhauser Effect Study of Macrolide-Ribosome Interactions: Correlation between Antibiotic Activities and Bound Conformations. Bioorg. Med. Chem. 1998, 6, 209-221.
20. 1H NMR Study. J. Chem. Soc., Perkin Trans. 2 2000, 1645-1652.
21. Studies have suggested that the hydrophobic nature of the macrolide bottom face is maintained in the ketolides. (a) Bertho, G.; Gharbi-Benarous, J.; Delaforge, M.; Lang, C.; Parent, A.; Girault, J.-P. Conformational Analysis of Ketolide, Conformations of RU 004 in Solution and Bound to Bacterial Ribosomes. J. Med. Chem. 1998, 41, 3373-3386.
22. (b) Evrard-Todeschi, N.; Gharbi-Benarous, J.; Gaillet, C.; Verdier, L.; Berthe, G.; Lang, C.; Parent, A.; Girault, J.-P. Conformations in Solution and Bound to Bacterial Ribosomes of Ketolides, HMR 3647 (Telithromycin) and RU 72366: A New Class of Highly Potent Antibacterials. Bioorg. Med. Chem. 2000, 8. 1579-1597.
23. (a) Burger, M.; Lin, X.; Chu, D.; Rico, A.; Hiebert, C.; Seid, M.; Carroll, G.; Barker, L.; Shawar, R.; Syntheses and in Vitro Antibacterial Activity of Novel Alkenyl and Alkynyl Ketolides. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003; Abstract F-1200.
24. (b) Chu, D.; Barker, L.; Shawar, R.; Langhorne, M.; Huh, K.; Burger, M.; Lin, X.; Carrol, G.; Fang, L.; Anderson, S.; Kidney, J.; Steffen, L.; Young, K. CHIR 380 and CHIR 988: Two Novel Potent Ketolides. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. 2003; Abstract F-1202.
25. (a) Baker, W. R.; Clark, J. D.; Stephens, R. L.; Kim, K. H. Modifications of Macrolide Antibiotics. Synthesis of 11-Deoxy-11-(carboxyamino)-6-O- methylerythromycin A 11,12-(Cyclic esters) via Intramolecular Michael Reaction of O-Carbamates with an α,β-Unsaturated Ketone. J. Org. Chem. 1988. 53, 2340-2345.
26. ( b) Fernandes, P. B.; Baker, W. R.; Freiberg, L. A.; Hardy, D. J.; McDonald, E. J. New Macrolides Active against Streptococcus pyogenes with Inducible or Constitutive Type of Macrolide-Lincosamide-Streptogramin B Resistance. Antimicrob. Agents Chemother. 1989. 33, 78-81.
27. (c) Elliott, R. L.; Pireh, D.; Griesgraber, G.; Nilius, A. M.; Ewing, P. J.; Bui, M. H.; Raney, P. M.; Flamm, R. K.; Kim, K.; Henry, R. F.; Chu, D. T. W.; Plattner, J. J.; Or, Y. S. Anhydrolide Macrolides. 1. Synthesis and Antibacterial Activity of 2,3-Anhydro-6-O-methyl-11,12-carbamate Erythromycin A Analogues. J. Med. Chem. 1998, 41, 1651-1659.
28. (d) Griesgraber, G.; Kramer, M. J.; Elliott, R. L.; Nilius, A. M.; Ewing, P. J.; Raney, P. M.; Bui, M.-H.; Flamm, R. K.; Chu, D. T. W.; Plattner, J. J.; Or, Y. S. Anhydrolide Macrolides. 2. Synthesis and Antibacterial Activity of 2,3-Anhydro-6-O-methyl-11,12-carbazate Erythromycin A Analogues. J. Med. Chem. 1998, 41, 1660-1670.
29. ( e) Hunziker, D.; Wyss, P. C.; Angehrn, P.; Mueller, A.; Marty, H. P.; Halm, R.; Kellenberger, L.; Bitsch. V.; Biringer, G.; Arnold, W.; Stämpfli, A.; Schmitt-Hoffmann, A.; Cousot, D. Novel Ketolide Antibiotics with a Fused Five-Membered Lactone Ring-Synthesis, Physicochemical and Antimicrobial Properties. Bioorg. Med. Chem. 2004, 12, 3503-3519.
30. Su, W. G.; Smyth, K. T.; Rainville, J. P.; Kaneko, T.; Sitcliffe, J. S.; Brennan, L. A.; Duignan, J. M.; Girard, A. E.; Finegan, S. M.; Cimochowski, C. R. Novel Erythromycin 4-Carbamate Antibacterial Agents: Synthesis and Biological Evaluation Resulting in Discovery of CP-544372. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy 1998; Abstract F-122
31. (a) Macielag, M.; Abbanat, D.; Ashley, G.; Foleno, B.; Fu, H.; Li. Y.; Wira, E.; Bush, K. Structure-Activity Studies of 15-Methyl Ketolides: Optimization of the Heterocyclic Substituent. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego, CA, 2002; Abstract F-1662.
32. (b) Abbanat, D.; Ashley, G.; Foleno, B.; Fu, H.; Hilliard, J.; Li, Y.; Licari, P.; Macielag, M.; Melton, J.; Monteenegro, D.; Raina, D.; Stryker, S.; Wira, E. J.; Bush. K. In Vitro and in Vivo Antibacterial Activities of 15-Methyl-2-fluoro Ketolides. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003; Abstract F-1203.
33. th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2004; Abstract F-1409.
34. (a) Or, Y. S.; Wang, G.; Phan, L. T.; Niu, D.; Vo, N. H.; Qiu, Y.; Wang, Y.; Busuyek, M.; Hou, Y.; Peng, Y.; Kim, H.; Liu, T.; Farmer, Jay, J.; Xu, G. Preparation of 6-11 bicyclic erythromycin ketolide derivatives as antibacterial agents. U.S. Patent No. 6,878,691 B2. April 12, 2005.
35. (b) Scorneaux, B.; Arya, A.; Polemeropoulos, A.; Lillard, M.; Han, F.; Amsler, K.; Sonderfan, A.; Wang, G.; Wang, Y.; Peng, Y.; Xu, G.; Kim, H.; Lien, T.; Phan, L.; Or, Y. T. In vitro and in Vivo Evaluation of EP-13420: A Novel Ketolide Highly Active against Resistant Pathogens and Having Exceptional Pharmacokinetic Properties in the Dog. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003; Abstract F-1191.
36. Hauske, J. R.; Guadliana, M.; Kostek, G.; Schulte, G. Aglycon Modifications of Erythromycin A: Regiospecific and Stereospecific Elaboration of the C-12 Position. J. Org. Chem. 1987, 52, 4622-4625.
37. Lartey, P. A.; DeNinno, S. L.; Faghih, R.; Hardy, D. J.; Clement, J. J.; Plattner, J. J. Synthesis and Activity of C-21 Alkylamino Derivatives of (9R)-Erythromycylamine. J. Antihiot. 1992, 45, 380-385.
38. Bernet, B.; Bishop, P. M.; Caron, M.; Kawamat, T.; Roy, B. L.; Ruest, L.; Soucy, P.; Deslongchamps, P. Formal Total Synthesis of Erythromycin A. Part II. Preparation of a 1,7-Dioxapiro[5,5]undecane Derivative of Erythronolide A Seco Acid Methyl Ester from Erythromycin A. Can. J. Chem. 1985, 63, 2814-2818.
39. (a) Sharpless, K. B.; Akashi, K. Osmium Catalyzed Vicinal Hydroxylation of Olefins by Terr-Butyl Hydroperoxide under Alkaline Conditions. J. Am. Chem. Soc. 1976, 98, 1986-1987.
40. 4 Hydroxylation of Olefins to Cis-1,2 Glycols Using Tertiary Amine Oxides as the Oxidant. Tetrahedron Lett. 1976, 1973-1976.
41. Martin, J. C.; Dess, D. B. A Useful 12-1-5 Triacetoxyperiodinane (The Dess-Martin Periodinane) for the Selective Oxidation of Primary or Secondary Alcohols and a Variety of Related 12-1-5 Species. J. Am. Chem. Soc. 1991. 113, 7277-7287.
42. Corey, E. J.; Kim, C. U. New and Highly Effective Method for the Oxidation of Primary and Secondary Alcohols to Carbonyl Compounds. J. Am. Chem. Soc. 1972, 94, 7586-7587.
43. 1H NMR spectra see Supporting Information. (22) Xiadong Lin, unpublished results.
44. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard, 6th ed.; NCCLS document M7-A6; NCCLS: Wayne, PA, 2003.
45. Performance Standards for Antimicrobial Susceptibility Testing; Approved Standard; 14th ed.; NCCLS document M100-S13; NCCLS: Wayne, PA, 2003.