Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphylococcus aureus strains possessing the cfr methyltransferase gene or ribosomal mutations

Antimicrobial Agents and Chemotherapy

Volumn 54, Issue 12, 2010, Pages 5337-5343

  Locke, Jeffrey B ^a   Finn, John ^a   Hilgers, Mark ^a   Morales, Gracia ^b   Rahawi, Shahad ^a   Kedar, G C ^a   Picazo, Juan José ^b   Im, Weonbin ^c   Shaw, Karen Joy ^a   Stein, Jeffrey L ^a  

^a Trius Therapeutics Inc   (United States)

^b HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^c Dong A Pharmaceutical Company   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ACETAMIDE; LINEZOLID; METHYLTRANSFERASE; OXAZOLIDINONE DERIVATIVE; PEPTIDYLTRANSFERASE; RADEZOLID; RX 1741; TOREZOLID; TR 700; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENE; BACTERIAL STRAIN; CFR GENE; DRUG POTENCY; GENE MUTATION; NONHUMAN; PRIORITY JOURNAL; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

ACETAMIDES; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; METHYLTRANSFERASES; MICROBIAL SENSITIVITY TESTS; MUTATION; OXAZOLIDINONES; RIBOSOMES; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78649668302     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00663-10     Document Type: Article

References (79)

1. Ament, P. W., N. Jamshed, and J. P. Horne. 2002. Linezolid: its role in the treatment of Gram-positive, drug-resistant bacterial infections. Am. Fam. Physician 65:663-670.
2. Arias, C. A., M. Vallejo, J. Reyes, D. Panesso, J. Moreno, E. Castaneda, M. V. Villegas, B. E. Murray, and J. P. Quinn. 2008. Clinical and microbiological aspects of linezolid resistance mediated by the cfr gene encoding a 23S rRNA methyltransferase. J. Clin. Microbiol. 46:892-896.
3. Auerbach, T., I. Mermershtain, C. Davidovich, A. Bashan, M. Belousoff, I. Wekselman, E. Zimmerman, L. Xiong, D. Klepacki, K. Arakawa, H. Kinashi, A. S. Mankin, and A. Yonath. 2010. The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics. Proc. Natl. Acad. Sci. U. S. A. 107:1983-1988.
4. Baker, C. N., and F. C. Tenover. 1996. Evaluation of Alamar colorimetric broth microdilution susceptibility testing method for staphylococci and enterococci. J. Clin. Microbiol. 34:2654-2659.
5. Barbachyn, M. R., and C. W. Ford. 2003. Oxazolidinone structure-activity relationships leading to linezolid. Angew. Chem. Int. Ed. Engl. 42:2010-2023.
6. Barbachyn, M. R., D. K. Hutchinson, S. J. Brickner, M. H. Cynamon, J. O. Kilburn, S. P. Klemens, S. E. Glickman, K. C. Grega, S. K. Hendges, D. S. Toops, C. W. Ford, and G. E. Zurenko. 1996. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J. Med. Chem. 39:680-685.
7. Berisio, R., F. Schluenzen, J. Harms, A. Bashan, T. Auerbach, D. Baram, and A. Yonath. 2003. Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat. Struct. Biol. 10:366-370.
8. Bonilla, H., J. P. Quinn, J. Siedel, H. Schmidt, M. Lescoe, S. P. McCurdy, M. M. Lemmon, M. D. Huband, L. Puzniak, T. Hart, K. Jafri, L. A. Brennan, and A. Tait-Kamradt. 2009. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother., abstr. C2-131.
9. Brickner, S. J., M. R. Barbachyn, D. K. Hutchinson, and P. R. Manninen. 2008. Linezolid (ZYVOX), the first member of a completely new class of antibacterial agents for treatment of serious gram-positive infections. J. Med. Chem. 51:1981-1990.
10. Brickner, S. J., D. K. Hutchinson, M. R. Barbachyn, P. R. Manninen, D. A. Ulanowicz, S. A. Garmon, K. C. Grega, S. K. Hendges, D. S. Toops, C. W. Ford, and G. E. Zurenko. 1996. Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. J. Med. Chem. 39:673-679.
11. Burleson, B. S., D. J. Ritchie, S. T. Micek, and W. M. Dunne. 2004. Enterococcus faecalis resistant to linezolid: case series and review of the literature. Pharmacotherapy 24:1225-1231.
12. Campanile, F., D. Bongiorno, S. Borbone, G. Mongelli, M. Baldi, R. Provenzani, and S. Stefani. 2009. Abstr. 19th Eur. Congr. Clin. Microbiol. Infect. Dis., abstr. P929. European Society of Clinical Microbiology and Infectious Diseases, Munich, Germany.
13. Cercenado, E., M. Marín, R. Insa, and E. Bouza. 2010. Abstr. 20th Eur. Congr. Clin. Microbiol. Infect. Dis., abstr. P1104. European Society of Clinical Microbiology and Infectious Diseases, Munich, Germany.
14. CLSI. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard, CLSI document M7-A7, 7th ed., vol. 26, no. 2. CLSI, Wayne, PA.
15. Davidovich, C., A. Bashan, T. Auerbach-Nevo, R. D. Yaggie, R. R. Gontarek, and A. Yonath. 2007. Induced-fit tightens pleuromutilins binding to ribosomes and remote interactions enable their selectivity. Proc. Natl. Acad. Sci. U. S. A. 104:4291-4296.
16. DeLano, W. L. 2002. The PyMOL molecular graphics system. DeLano Scientific, Palo Alto, CA.
17. Engemann, J. J., M. J. Joyce, L. J. Harrell, S. Evans, L. Reller, and D. Sexton. 2003. Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1112. American Society for Microbiology, Washington, DC.
18. Farrell, D. J., R. E. Mendes, J. E. Ross, and R. N. Jones. 2009. Linezolid surveillance program results for 2008 (LEADER Program for 2008). Diagn. Microbiol. Infect. Dis. 65:392-403.
19. Fritsche, T. R., M. Castanheira, R. E. Mendes, R. N. Jones, and L. M. Deshpande. 2008. Abstr. 108th Gen. Meet. Am. Soc. Microbiol., abstr. A-047. American Society for Microbiology, Washington, DC.
20. Genin, M. J., D. A. Allwine, D. J. Anderson, M. R. Barbachyn, D. E. Emmert, S. A. Garmon, D. R. Graber, K. C. Grega, J. B. Hester, D. K. Hutchinson, J. Morris, R. J. Reischer, C. W. Ford, G. E. Zurenko, J. C. Hamel, R. D. Schaadt, D. Stapert, and B. H. Yagi. 2000. Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J. Med. Chem. 43:953-970.
21. Giessing, A. M., S. S. Jensen, A. Rasmussen, L. H. Hansen, A. Gondela, K. Long, B. Vester, and F. Kirpekar. 2009. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15:327-336.
22. Gonzales, R. D., P. C. Schreckenberger, M. B. Graham, S. Kelkar, K. DenBesten, and J. P. Quinn. 2001. Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. Lancet 357:1179.
23. Gravestock, M. B., D. G. Acton, M. J. Betts, M. Dennis, G. Hatter, A. McGregor, M. L. Swain, R. G. Wilson, L. Woods, and A. Wookey. 2003. New classes of antibacterial oxazolidinones with C-5, methylene O-linked heterocyclic side chains. Bioorg. Med. Chem. Lett. 13:4179-4186.
24. Gravestock, M. B., N. J. Hales, F. Reck, and F. Zhou. 3 March 2009. Oxazolidinones as antibacterial agents. U.S. patent 7,498,350 B2.
25. Gregory, W. A., D. R. Brittelli, C. L. Wang, H. S. Kezar III, R. K. Carlson, C. H. Park, P. F. Corless, S. J. Miller, P. Rajagopalan, M. A. Wuonola, et al. 1990. Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 2. The "A" group. J. Med. Chem. 33:2569-2578.
26. Gregory, W. A., D. R. Brittelli, C. L. Wang, M. A. Wuonola, R. J. McRipley, D. C. Eustice, V. S. Eberly, P. T. Bartholomew, A. M. Slee, and M. Forbes. 1989. Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 1. The "B" group. J. Med. Chem. 32:1673-1681.
27. Harms, J. M., F. Schlunzen, P. Fucini, H. Bartels, and A. Yonath. 2004. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2:4.
28. Holzel, C. S., K. S. Harms, K. Schwaiger, and J. Bauer. 2010. Resistance to linezolid in a porcine Clostridium perfringens strain carrying a mutation in the rplD gene encoding the ribosomal protein L4. Antimicrob. Agents Chemother. 54:1351-1353.
29. Im, W., S. Choi, and J. Rhee. 2007. Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F1-1686. American Society for Micriobiology, Washington, DC.
30. Ippolito, J. A., Z. F. Kanyo, D. Wang, F. J. Franceschi, P. B. Moore, T. A. Steitz, and E. M. Duffy. 2008. Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit. J. Med. Chem. 51:3353-3356.
31. Jo, Y. W., W. B. Im, J. K. Rhee, M. J. Shim, W. B. Kim, and E. C. Choi. 2004. Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring. Bioorg. Med. Chem. 12:5909-5915.
32. Jones, R. N., S. Kohno, Y. Ono, J. E. Ross, and K. Yanagihara. 2009. ZAAPS International Surveillance Program (2007) for linezolid resistance: results from 5591 Gram-positive clinical isolates in 23 countries. Diagn. Microbiol. Infect. Dis. 64:191-201.
33. Jones, R. N., G. J. Moet, H. S. Sader, R. E. Mendes, and M. Castanheira. 2009. TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens. J. Antimicrob. Chemother. 63:716-720.
34. Jones, R. N., J. E. Ross, J. M. Bell, U. Utsuki, I. Fumiaki, I. Kobayashi, and J. D. Turnidge. 2009. Zyvox Annual Appraisal of Potency and Spectrum Program: linezolid surveillance program results for 2008. Diagn. Microbiol. Infect. Dis. 65:404-413.
35. Kehrenberg, C., C. Cuny, B. Strommenger, S. Schwarz, and W. Witte. 2009. Methicillin-resistant and -susceptible Staphylococcus aureus strains of clonal lineages ST398 and ST9 from swine carry the multidrug resistance gene cfr. Antimicrob. Agents Chemother. 53:779-781.
36. Kehrenberg, C., S. Schwarz, L. Jacobsen, L. H. Hansen, and B. Vester. 2005. A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503. Mol. Microbiol. 57:1064-1073.
37. Komine, T., A. Kojima, Y. Asahina, T. Saito, H. Takano, T. Shibue, and Y. Fukuda. 2008. Synthesis and structure-activity relationship studies of highly potent novel oxazolidinone antibacterials. J. Med. Chem. 51:6558-6562.
38. LaMarre, J. M., T. Zhu, J. B. Locke, K. J. Shaw, and A. S. Mankin. 2009. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother., abstr. C1-1346. American Society for Microbiology, Washington, DC.
39. Lawrence, L., P. Danese, J. DeVito, F. Franceschi, and J. Sutcliffe. 2008. In vitro activities of the Rx-01 oxazolidinones against hospital and community pathogens. Antimicrob. Agents Chemother. 52:1653-1662.
40. Leach, K. L., S. M. Swaney, J. R. Colca, W. G. McDonald, J. R. Blinn, L. M. Thomasco, R. C. Gadwood, D. Shinabarger, L. Xiong, and A. S. Mankin. 2007. The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol. Cell 26:393-402.
41. Livermore, D. M., S. Mushtaq, M. Warner, and N. Woodford. 2009. Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci. J. Antimicrob. Chemother. 63:713-715.
42. Locke, J. B., M. Hilgers, and K. J. Shaw. 2009. Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin. Antimicrob. Agents Chemother. 53:5275-5278.
43. Locke, J. B., M. Hilgers, and K. J. Shaw. 2009. Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700). Antimicrob. Agents Chemother. 53:5265-5274.
44. Locke, J. B., A. S. Mankin, J. LaMarre, V. Brown-Driver, and K. J. Shaw. 2009. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother., abstr. C1-1364b. American Society for Microbiology, Washington, DC.
45. Locke, J. B., G. Morales, M. Hilgers, K. G. C., S. Rahawi, J. J. Picazo, K. J. Shaw, and J. L. Stein. 2010. Elevated linezolid resistance in clinical cfr-positive Staphylococcus aureus isolates is associated with co-occurring mutations in ribosomal protein L3. Antimicrob. Agents Chemother. 54:5352-5355.
46. Long, K. S., J. Poehlsgaard, C. Kehrenberg, S. Schwarz, and B. Vester. 2006. The cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob. Agents Chemother. 50:2500-2505.
47. Mendes, R. E. 2009. Abstr. 19th European Congress of Clinical Microbiology and Infectious Diseases, abstr. O96. European Society of Clinical Microbiology and Infectious Diseases, Munich, Germany.
48. Mendes, R. E. 2009. Abstr. 19th European Congress of Clinical Microbiology and Infectious Diseases, abstr. P928. European Society of Clinical Microbiology and Infectious Diseases, Munich, Germany.
49. Mendes, R. E., L. M. Deshpande, M. Castanheira, J. Dipersio, M. Saubolle, and R. N. Jones. 2008. First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob. Agents Chemother. 52:2244-2246.
50. Morales, G., and J. J. Picazo. 2009. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother., abstr. E-808. American Society for Microbiology, Washington, DC.
51. Morales, G., J. J. Picazo, E. Baos, F. J. Candel, A. Arribi, B. Pelaez, R. Andrade, M. A. de la Torre, J. Fereres, and M. Sanchez-Garcia. 2010. Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin. Infect. Dis. 50:821-825.
52. Overbye, K. M., and D. Mordekhay. 2007. AM-7359 - a novel oxazolidinone with low resistance potential and potent activity against drug resistant pathogens. J. Chemother. 19:249-255.
53. Paget, S. D., B. D. Foleno, C. M. Boggs, R. M. Goldschmidt, D. J. Hlasta, M. A. Weidner-Wells, H. M. Werblood, E. Wira, K. Bush, and M. J. Macielag. 2003. Synthesis and antibacterial activity of pyrroloaryl-substituted oxazolidinones. Bioorg. Med. Chem. Lett. 13:4173-4177.
54. Park, C. H., D. R. Brittelli, C. L. Wang, F. D. Marsh, W. A. Gregory, M. A. Wuonola, R. J. McRipley, V. S. Eberly, A. M. Slee, and M. Forbes. 1992. Antibacterials. Synthesis and structure-activity studies of 3-aryl-2- oxooxazolidines. 4. Multiply-substituted aryl derivatives. J. Med. Chem. 35:1156-1165.
55. Phillips, O. A., E. E. Udo, A. A. Ali, and N. Al-Hassawi. 2003. Synthesis and antibacterial activity of 5-substituted oxazolidinones. Bioorg. Med. Chem. 11:35-41.
56. Reck, F., F. Zhou, C. J. Eyermann, G. Kern, D. Carcanague, G. Ioannidis, R. Illingworth, G. Poon, and M. B. Gravestock. 2007. Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility. J. Med. Chem. 50:4868-4881.
57. Reck, F., F. Zhou, M. Girardot, G. Kern, C. J. Eyermann, N. J. Hales, R. R. Ramsay, and M. B. Gravestock. 2005. Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A. J. Med. Chem. 48:499-506.
58. Renslo, A. R., G. W. Luehr, and M. F. Gordeev. 2006. Recent developments in the identification of novel oxazolidinone antibacterial agents. Bioorg. Med. Chem. 14:4227-4240.
59. Schenk, S., and R. A. Laddaga. 1992. Improved method for electroporation of Staphylococcus aureus. FEMS Microbiol. Lett. 73:133-138.
60. Schlünzen, F., J. M. Harms, F. Franceschi, H. A. Hansen, H. Bartels, R. Zarivach, and A. Yonath. 2003. Structural basis for the antibiotic activity of ketolides and azalides. Structure 11:329-338. (Pubitemid 36287695)
61. Schlünzen, F., E. Pyetan, P. Fucini, A. Yonath, and J. M. Harms. 2004. Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin. Mol. Microbiol. 54:1287-1294.
62. Schlunzen, F., R. Zarivach, J. Harms, A. Bashan, A. Tocilj, R. Albrecht, A. Yonath, and F. Franceschi. 2001. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413:814-821.
63. Shaw, K. J., S. Poppe, R. Schaadt, V. Brown-Driver, J. Finn, C. M. Pillar, D. Shinabarger, and G. Zurenko. 2008. In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains. Antimicrob. Agents Chemother. 52:4442-4447.
64. Skripkin, E., T. S. McConnell, J. Devito, L. Lawrence, J. A. Ippolito, E. M. Duffy, J. Sutcliffe, and F. Franceschi. 2008. Rx-01: a new family of oxazolidinones that overcomes ribosomal-based linezolid resistance. Antimicrob. Agents Chemother. 52:3550-3557.
65. Slee, A. M., M. A. Wuonola, R. J. McRipley, I. Zajac, M. J. Zawada, P. T. Bartholomew, W. A. Gregory, and M. Forbes. 1987. Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob. Agents Chemother. 31:1791-1797.
66. Smith, L. K., and A. S. Mankin. 2008. Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors. Antimicrob. Agents Chemother. 52:1703-1712.
67. Swaney, S. M., H. Aoki, M. C. Ganoza, and D. L. Shinabarger. 1998. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Antimicrob. Agents Chemother. 42:3251-3255.
68. Toh, S. M., L. Xiong, C. A. Arias, M. V. Villegas, K. Lolans, J. Quinn, and A. S. Mankin. 2007. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol. Microbiol. 64:1506-1514.
69. Tsiodras, S., H. S. Gold, G. Sakoulas, G. M. Eliopoulos, C. Wennersten, L. Venkataraman, R. C. Moellering, and M. J. Ferraro. 2001. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 38:207-208.
70. Tu, D., G. Blaha, P. B. Moore, and T. A. Steitz. 2005. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 121:257-270.
71. Vara Prasad, J. V. 2007. New oxazolidinones. Curr. Opin. Microbiol. 10:454-460.
72. Venkatachalam, C. M., X. Jiang, T. Oldfield, and M. Waldman. 2003. LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. J. Mol. Graph. Model. 21:289-307.
73. Wilson, D. N., F. Schluenzen, J. M. Harms, A. L. Starosta, S. R. Connell, and P. Fucini. 2008. The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc. Natl. Acad. Sci. U. S. A. 105:13339-13344.
74. Wilson, P., J. A. Andrews, R. Charlesworth, R. Walesby, M. Singer, D. J. Farrell, and M. Robbins. 2003. Linezolid resistance in clinical isolates of Staphylococcus aureus. J. Antimicrob. Chemother. 51:186-188.
75. Wolter, N., A. M. Smith, D. J. Farrell, W. Schaffner, M. Moore, C. G. Whitney, J. H. Jorgensen, and K. P. Klugman. 2005. Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Antimicrob. Agents Chemother. 49:3554-3557.
76. Wong, A., S. P. Reddy, D. S. Smyth, M. E. Aguero-Rosenfeld, G. Sakoulas, and D. A. Robinson. 2010. Polyphyletic emergence of linezolid-resistant staphylococci in the United States. Antimicrob. Agents Chemother. 54:742-748.
77. Yong, D., J. H. Yum, K. Lee, Y. Chong, S. H. Choi, and J. K. Rhee. 2004. In vitro activities of DA-7867, a novel oxazolidinone, against recent clinical isolates of aerobic and anaerobic bacteria. Antimicrob. Agents Chemother. 48:352-357.
78. Zhou, J., A. Bhattacharjee, S. Chen, Y. Chen, E. Duffy, J. Farmer, J. Goldberg, R. Hanselmann, J. A. Ippolito, R. Lou, A. Orbin, A. Oyelere, J. Salvino, D. Springer, J. Tran, D. Wang, Y. Wu, and G. Johnson. 2008. Design at the atomic level: design of biaryloxazolidinones as potent orally active antibiotics. Bioorg. Med. Chem. Lett. 18:6175-6178.
79. Zhou, J., A. Bhattacharjee, S. Chen, Y. Chen, E. Duffy, J. Farmer, J. Goldberg, R. Hanselmann, J. A. Ippolito, R. Lou, A. Orbin, A. Oyelere, J. Salvino, D. Springer, J. Tran, D. Wang, Y. Wu, and G. Johnson. 2008. Design at the atomic level: generation of novel hybrid biaryloxazolidinones as promising new antibiotics. Bioorg. Med. Chem. Lett. 18:6179-6183.