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Chapter 1 : Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not

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Abstract:

The review by Domagala in 1994 represented one of the first attempts to simultaneously delineate the structure-activity relationships (SARs) of both activity and side effects providing some insights as to where the future of the quinolones might reside. A significant conclusion of this work was that the side chain at C-7 in conjunction with that at C-8 would be the main focus of successful quinolone manipulation; all other positions were viewed as optimal. The chiral form of the fluorocyclopropyl group slightly affects the overall antibacterial activity, with a two- to four-fold difference in potency between the most active stereoisomer and the least active; overall, the isomer was more efficacious than the isomer. The 2 pyridones, which were introduced in 1994, represent a new structural class of "quinolone-type" antibacterials. The fluoroquinolones derived their name from the dogma that the 6-fluoro group was an essential feature of the broad-spectrum quinolones that first appeared in the late 1970s. Extensive SAR work on 7-(3-amino)-azetidinyl quinolones such as E-4695 (structure 35) has been reported. Initial success with the 3-amino derivatives led to further exploration of 2-alkyl-3-amino analogs (structure 36) with particular emphasis on the effects of stereochemistry on antibacterial activity. The reality of the quinolone SAR efforts is that all the potency ever required was already in hand in the early 1990s.

Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
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References

/content/book/10.1128/9781555817817.chap1
1. Allemandi, D. A.,, F. L. Alovero,, and R. Manzo. 1994. Invitro activity of new sulphanilil fluoroquinolones against Staphylococcus aureus. J. Antimicrob. Chemother. 34:261265.
2. Alovero, F. L.,, X.-S. Pan,, J. E. Morris,, R. H. Manzo,, and L. M. Fisher. 2000. Engineering the specificity of antibacterial fluoroquinolones: benzenesulfonamide modifications at C-7 of ciprofloxacin change its primary target in Streptococcus pneumonia from topoisomerase IV to gyrase. Antimicrob. Agents Chemother. 44:320325.
3. Amano, H.,, N. Hayashi,, Y. Ohshita,, Y. Niino,, and A. Yazaki. 1997. WQ-2724 and WQ-2743, Novel fluoroquinolones: in vitro and in vivo activities, pharmacokinetics and toxicity, Abstr. F-163. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy , Toronto, Canada.
4. Applebaum, P. C.,, and P. A. Hunter. 2000. The fluoroquinolone antibacterials: past, present, and future perspectives. Int. J. Antibacter. Agents 515.
5. Armiger, Y. L.,, D. T. W. Chu,, A. K. L. Fung,, Q. Li,, W. Wang,, A. Nilius,, J. Alder,, P. Ewing,, G. Stone,, J. Meulbroek,, M. Bui,, L. L. Shen,, L. Paige,, Y. S. Or,, and J. J. Plattner. 1998. The discovery of A-165753 and 170568, two potent broad spectrum antimicrobial agents, abstr. F-86. In Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
6. Ball, P.,, A. Fernald,, and G. Tillotson. 1998. Therapeutic advances of new fluoroquinolones. Exp. Opin. Investig. Drugs 7:761783.
7. Barry, A. L.,, P. C. Fuchs,, and S. D. Brown. 2001. In vitro activities of three nonfluorinated quinolones against representative bacterial isolates. Antimicrob. Agents Chemother. 45:19231927.
8. Bierman, J.,, D. Reichart,, J. Emig,, H. McKeever,, B. Kuzmak,, M. Gazda,, and B. Ledoussal. 1999. In vivo efficacy of a series of non-fluoroquinolones (NFQ's) in mice, Abstr. F- 551. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
9. Bouzard, D.,, P. D. Cesare,, M. Essiz,, J. P. Jacquet,, B. Ledoussal,, P. Remuzon,, R. E. Kessler,, and J. Fung-Tome. 1992. Fluoronaphthyridines as antibacterial agents. 4. Synthesis and structure-activity relationships of 5-substituted 6-fluoro-7-(cycIoalkylamino)-l,4-dihydro-4-oxo-l,8-naphthyri dine-3-carboxylic acids./. Med. Chem. 35:518525.
10. Brown, S. D.,, A. L. Barry,, and P. C. Fuchs. 1999. In vitro antibacterial activity of a series of novel non-fluoroquinolones (NFQ's) against bacterial pathogens, abstr. F- 549. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
11. Bryskier, A.,, and J.-F. Chantot. 1995. Classification and structure-activity relationships of fluoroquinolones. Drugs 49(Suppl. 2):1628.
12. Cecchetti, V.,, S. Clementi,, G. Cruciani,, A. Fravolini,, P. G. Pagella,, A. Savino,, and O. Tabarrini. 1995. 6- Aminoquinolones: a new class of quinolone antibacterials? J. Med. Chem. 38:973982.
13. Cecchetti, V.,, A. Fravolini,, M. C. Lorenzini,, O. T.,, P. Terni,, and T. Xin. 1996. Studies on 6-aminoquinolones: synthesis and antibacterial evaluation of 6-amino-8-methylquinolones. J. Med. Chem. 39:436445.
14. Chu, D. T. W.,, P. B. Fernandes,, A. K. Claiborne,, E. Pihuleac,, C. W. Nordeen,, R. E. Maleczka, Jr.,, and A. G. Pernet. 1985. Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents. J. Med. Chem. 28:15581564.
15. Chung, S. J.,, and D. H. Kim. 1997. Synthesis and evaluation of 3-fluoro-2-piperazinyl-5,6,13-trihydro-5-oxoquino[l,2- a][3,l]benzox azine-6-carboxylic acids as potential antibacterial agents. Arch. Pharm. Med. Chem. 330:6366.
16. Ciaravino, V.,, M. J. Suto,, and J.C. Theiss. 1993. High capacity in vitro micronucleus assay for assessment of chromosome damage: Results with quinolone /napthyridone antibacterials. Mutat. Res. 298:227236.
17. De Sarro, A.,, V. Cecchetti,, V. Fravolini,, F. Naccari,, O. Tabarrini,, and G. De Sarro. 1999. Effects of novel 6-desfluoroquinolones and classic quinolones on pentylenetetrazoleinduced seizures in mice. Antimicrob. Agents Chemother. 43:17291736.
18. Domagala, J. M. 1994. Review: structure-activity and structure- side-effect relationships for the quinolone antibacterials. J. Antimicrob. Chemother. 33:685706.
19. Domagala, J. M.,, A. J. Bridges,, T. P. Culbertson,, L. Gambino,, S. E. Hagen,, G. Karrick,, K. Porter,, J. P. Sanchez,, J. A. Sesnie,, F. G. Spense,, D. D. Szotek,, and J. Wemple. 1991. Synthesis and biological activity of 5-amino- and 5- hydroxyquinolones, and the overwhelming influence of the remote Nj. substituent in determining the structure-activity relationship.J. Med. Chem. 34:11421154.
20. Domagala, J. M.,, S. E. Hagen,, M. P. Hutt,, J. P. Sanchez,, J. Sesnie,, and A. K. Trehan. 1988. 5-Amino-7-(3-amino-lpyrrolidinyl)- l-cyclopropyl-6,8-difluoro-l,4-dihydro-4 - oxo-3-quinolinecarboxylic acid (PD 124,816). Synthesis and biological evaluation of a new class of quinolone antibacterials. Drugs Exp. Clin. Res. 14:453460.
21. Domagala, J. M.,, S. E. Hagen,, T. Joannides,, J. S. Kiely,, E. Laborde,, M. C. Schroeder,, J. A. Sesnie,, M. A. Shapiro,, M. J. Suto,, and S. Vanderroest. 1993. Quinolone antibacterials containing the new 7-[3-(l-aminoethyl)-l-pyrroldinyl] side chain: the effects of the 1-aminoethyl moiety and its stereochemical configurations on potency and in vivo efficacy.J. Med. Chem. 36:871882.
22. Domagala, J. M.,, L. D. Hanna,, C. L. Heifetz,, M. P. Hutt,, T. F. Mich,, J. P. Sanchez,, and M. Solomon. 1986. New structure- activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J. Med. Chem. 29:394404.
23. Dougherty, T. J.,, D. Beulieu,, and J. F. Barrett. 2001. New quinolones and the impact on resistance. Drug Disc. Today 6:529536.
24. Felmingham, D.,, M. J. Robbins,, C. Dencer,, I. Mathias,, H. Salman,, and G. L. Ridgway. 2000. Abstr. F-1511. In vitro activity of non-fluorinated quinolones (PGE-926932, -4175997, -9509924) against Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp., Abstr. F-1511. In Proceedings of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
25. Foroumadi, A.,, S. Emami,, A. Davood,, H. Moshafi,, A. Sharifian,, M. Tabatabaie,, H. Farimanni,, S. G. Tarhimi,, and A. Shafiee. 1997. Synthesis and in-vitro antibacterial activities of N-substituted piperazinyl quinolones. Pharm. Sci. 3:559563.
26. Foroumadi, A.,, S. Emami,, P. Haghighat,, and M. H. Moshafi. 1999. Synthesis and in-vitro antibacterial activity of new N-substituted piperazinyl quinolones. Pharm. Pharmacol. Commun. 5:591594.
27. Frigola, J.,, A. Torrens,, J.A. Castrillo,, J. Mas,, D. Vano,, J. M. Berrocal,, C. Calvet,, L. Salgado,, J. Redondo,, S. Garcia- Granda,, E. Valenti,, and J. R. Quintana. 1994. 7- Azetidinylquinolones as antibacterial agents. 2. Synthesis and biological activity of 7-(2,3-disubstituted-l-azetidinyl)- 4-oxoquinoline- and-l,8-naphthyridine-3-carboxylic acids. Properties and structure-activity relationships of quinolones with an azetidine moiety.J. Med. Chem. 37:41954210.
28. Frigola, J.,, D. Vano,, A. Torrens,, A. Gomez-Gomar,, E. Ortega,, and S. Garcia-Granda. 1995. 7-Azetidinylquinolones as antibacterial agents. 3. Synthesis, properties, and structure-activity relationships of the stereoisomers containing a 7-(3-amino-2-methyl-l-azetidinyl) moiety.J. Med Chem. 38:12031215.
29. Fujita, M.,, K. Chiba,, J. Nakano,, Y. Tominaga,, and J.-I. Matsumoto. 1998. Synthesis and structure-antibacterial activity relationships of 7-(3-amino-l-propynyl and 3- amino-l-propenyl)quinolones. Chem. Pharm. Bull. 46:631638.
30. Fung, A. K. L.,, and L. L. Shen. 1999. The 2-pyridone antibacterial agents: 8-position modifications. Curr. Pharm. Design 5:515543.
31. Furuhata, K.,, H. Fukuda,, T. Nakamura,, Y. Morita,, H. Arai,, Y. Todo,, Y. Watanabe,, and H. Narita. 1999. Pharmacological evaluation of T-3811ME (BMS-284756): toxicity to the central nervous system, abstr. F-551. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D. C.
32. Furuhata, K.,, H. Fukuda,, A. Shimamoto,, H. Arai,, Y. Todo,, Y. Watanabe,, and H. Narita. 1998. Pharmacological evaluation of T-3811ME: toxicity on articular chondrocytes in vitro, abstr. F-77. In Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
33. Furuhata, K.,, K. Soumi,, J. Matsumoto,, A. Horikawa,, N. Nojima,, H. Arai,, Y. Todo,, Y. Watanabe,, and H. Narita. 1997. T-3811, a novel des-F(6)-quinolone: comparative studies of the adverse reactions associated with quinolones, abstr. F-161. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
34. Garcia-Rodriguez, J. A.,, J. E. Garcia Sanchez,, M. I. Garcia Garcia,, M. J. Fresnadillo,, I. Trujiliano,, and E. Garcia Sanchez. 1994. In-vitro activity of four new fluoroquinolones. J. Antimicrob. Chemother. 34:5364.
35. Granneman, G.R.,, K. M. Snyder,, and V. S. Shu. 1986. Difloxacin metabolism and pharmacokinetics in humans after single oral dose. Antimicrob. Agents and Chemother. 30:689693.
36. Gray, J. L.,, J. K. Almstead,, S. M. Flaim,, C. P. Gallagher,, X. E. Hu,, N. K. Kim,, H. D. McKeever,, C. J. Miley,, T. L. Twinem,, S. X. Zheng,, and B. Ledoussal. 2000. Synthesis and testing of non-fluorinated quinolones (NFQ's). A study on the influence of the C-6 position, abstr. F-1506. In Proceedings of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
37. Guinea, J.,, D. Gargallo-Viola,, M. Robert,, E. Tudela,, M. A. Xicota,, J. Garcia,, M. Esteve,, R. Coll,, M. Pares,, and R. Roser. 1995. E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens. Antimicrob. Agents Chemother. 39:413421.
38. Hagen, S. E.,, J. M. Domagala,, S. J. Gracheck,, J. A. Sesnie,, M. A. Stier,, and M. J. Suto. 1994. Synthesis and antibacterial activity of new quinolones containing a 7-[3-(l-amino-1- methylethyl)-l-pyrrolidinyl] moiety. Gram-positive agents with excellent oral activity and low side-effect profile.J. Med. Chem. 37:733738.
39. Hagen, S.,, J. M. Domagala,, C. L. Heifetz,, and J. Johnson. 1991. Synthesis and biological activity of 5-alkyl-l,7,8- trisubstituted—6-fluoroquinoline-3-carboxylic acids. J. Med. Chem. 34:11551161.
40. Hannon-Hardy, J.,, V. Murphy,, B. Kuzmak,, H. Murli,, P. Curry,, B. Ledoussal,, J. Gray,, S. Flaim,, N. Kim,, P. Young,, E. Swing,, N. Nikolaides,, S. Mundla,, M. Reilly,, and T. Schunk. 1999. Acute IV toxicity and clastogenicity of novel, 8- methoxy-non-fluoroquinolones compared to 8-methoxy-fluoroquinolones, abstr. F-553. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
40a. Hayashi, N.,, H. Amano,, Y. Ohshita,, Y. Niino,, J. Yoshida,, and A. Yazaki. 1996. In vitro and in vivo activities, pharmacokinetics and toxicity of WQ-2724 and WQ-2743, two novel fluoroquinolones, abstr. F-51. In Proceedings of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
41. Hayashi, N.,, Y. Hirao,, H. Amano,, Y. Oshita,, M. Yokomoto,, S. Inoue,, and A. Yazaki. 1995. WQ-0835, A prototypical tricyclic quinolone: in vitro and in vivo antibacterial activity and pharmacokinetics, abstr. F192. In Proceedings of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
41a. Hayashi, N.,, Y. Oshita,, H. Amano,, Y. Hirao,, Y. Niino,, and A. Yazaki. 1999. WQ-3330 and WQ-2942, structure-activity relationships of novel 8-methyl quinolones containing an aminophenyl group at the N-l position, abstr. 557. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
42. Hayashi, K.,, Y. Todo,, S. Hamamoto,, K. Ojima,, M. Yamada,, T. Kito,, M. Takahata,, Y. Watanabe,, and H. Narita. 1997. T-3811, a novel des-F(6)-quinolone: synthesis and in vitro activity of 7-(isoindolin-5-yl) derivatives, abstr. F-158. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
43. Hong, C. Y.,, Y. K. Kim,, J. H. Chang,, S. H. Kim,, H. Choi,, D. H. Nam,, Y. Z. Kim,, and J. H. Kwak. 1997. Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)pyrrolidin-l-yl)-lcyclopropyl- 6-fluoro- 4-oxo-l,4-dihydro[l,8]naphthyridine-3- carboxylic acids (LB 2 0 3 0 4 ) J. Med. Chem. 40:35841593.
44. Hong, C. Y.,, S. H. Kim,, and Y. K. Kim. 1997. Novel 5- amino-6-methylquinolone antibacterials: a new class of nonfluoroquinolones. Bioorg. Med. Chem. Lett. 7:18751878.
45. Hong, C. Y.,, Y. K. Kim,, J. H. Jang,, and M. Y. Kim. 1998. SB-265805 (LB20304a): Discovery of SB-265805, the synergistic effect of the methoxyloxime and aminomethyl groups of the C7-pyrrolidine on in vitro antibacterial activity, abstr. F-96. In Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
46. Hong, C. Y.,, Y. K. Kim,, D. H. Nam,, H. Choi,, J. H. Jang,, K. S. Paek,, and M. Y. Kim. 1998. SB-265805 (LB20304a): SAR of the oxime-derivatized pyrrolidine. The importance of the oximinoalkyl group on the in vitro antibacterial activity and pharmacokinetics, Abstr. F-95. In Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
47. Imamori, K. 1995. In vitro antibacterial activity of FA103, a new quinolone derivative of C-7 position with 7-perhydrodiazepinone. Jpn. J. Antibiot. 48:18911898.
48. Inoue, Y.,, H. Kondo,, M. Taguchi,, T. Jinbo,, F. Sakamoto,, and G. Tsukamoto. 1994. Synthesis and antibacterial activity of thiazolopyrazine-incorporated tetracyclic quinolone antibacterials.J. Med. Chem. 37:586592.
49. Ito, T.,, K. Kojima,, K. Koizuma,, H. Nagano,, and T. Nishino. 1994. Inhibitory activity on DNA gyrase and intracellular accumulation of quinolones: structure-activity relationship of Q-35 analogs. Biol. Pharm. Bull. 17:927930.
50. Jiraskova, N. 2000. Olamufloxacin. Curr. Opin. Investig. Drugs 1:3134.
51. Johnson, A. P. 1999. DW-116. Curr. Opin. Anti-lnfect. Investig. Drugs 1:488492.
52. Jung, B. H.,, M. H. Choi,, and B. C. Chung. 2000. Pharmacokinetics and urinary excretion of DW116, a new fluoroquinolone antibacterial agent, in humans as a Phase I study. Drug Dev. Ind. Pharm. 26:103106.
53. Jurgens, J.,, H. Schedletzky,, P. Heisig,, J. K. Seydel,, B. Wiedemann,, and U. Holzgrabe. 1996. Syntheses and biological activities of new Nt-aryl substituted quinolone antibacterials. Arch. Pharm. Pharm. Med. Chem. 329: 179190.
54. Kawamura, Y.,, A. Nagai,, M. Miyazaki,, T. Sanzen,, H. Fukumoto,, H. Hayakawa,, Y. Todo,, N. Terashima,, Y. Watanabe,, and H. Narita. 2000. Articular toxicity of BMS- 284756 (T-3811ME) administered orally to juvenile dogs, abstr. A-277. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
55. Kim, J.,, Y. H. Yoon,, I. H. Cho,, J. M. Lee,, K. Lee,, J. H. Kim,, and K. H. Hong. 1996. Synthesis and antibacterial activity of a new series of quinolones with 7-substituent of [3.1.1] bicyclic amines. Kor. J. Med. Chem. 6:183189.
56. Kim, J. H.,, J. A. Kang,, Y. G. Kim,, J. W. Kim,, J. H. Lee,, E. C. Choi,, and B. K. Kim. 1997. In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone. Antimicrob. Agents Chemother. 41:22092213.
57. Kim, O. K.,, J. F. Barrett,, and K. Ohemeng. 2001. Advances in DNA gyrase inhibitors. Exp. Opin. Investig. Drugs 10:199212.
58. Kim, S. H.,, Y. K. Kim,, H.-J. Kang,, and C. Y. Hong. 1997. Novel 6-methylquinolone antibacterials: a new class of non- 6-fluoroquinolones. J. Med. Chem. 7:1922.
59. Kimura, Y.,, S. Atarashi,, K. Kawakami,, K. Sato,, and I. Hayakawa. 1994. (Fluorocyclopropyl)quinolones. 2. Synthesis and stereochemical structure-activity relationships of chiral 7-(-amino-5-azaspiro[2,4]heptan-5-yl-)-l-(2-fluorocyclopropyl) quinolone antibacterial agents.J. Med. Chem. 37:33443352.
60. Kimura, Y.,, S. Atarashi,, M. Takahashi,, and I. Hayakawa. 1994. Synthesis and structure-activity relationships of 7-{3- (l-aminoalkyl)pyrrolidinyl]- and 7-[3-(l-aminocycloalkyl) pyrroldinyl]-quinolone antibacterials. Chem. Pharm. Bull. 42:14421454.
61. Kitzis, M. D.,, F. W. Goldstein,, N. Ishida,, and J. F. Acar. 1995. SYN987, SYN1193, and SYN1253, new quinolones highly active against gram-posiave cocci. J. Antimicrob. Chemother. 36:209213.
62. Klopman, G.,, D. Fercu,, T. E. Renau,, M. R. Jacobs. 1996. N-ltert- butyl-substituted quinolones: in vitro anti-Mycobacterium avium activities and structure-activity relationship studies. Antimicrob. Agents Chemother. 40:26372643.
63. Laborde, E.,, J. S. Kiely,, T. P. Culbertson,, and L. E. Lesheski. 1993. Quinolone antibacterials: synthesis and biological activity of carbon isosteres of the 1-piperazinyl and 3-amino-l-pyrroldinyl side chains. J. Med. Chem. 36:19641970.
64. Lawrence, L. E.,, P. G. Wu,, L. Fan,, K. Gouveia,, A. Card,, K. Denbleyker,, and J. F. Barrett. 2000. The structure-activity relationship of BMS-284756, a novel des-F(6)-quinolone, abstr. C-751. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
65. Ledoussal, B.,, J. K. Almstead,, S. M. Flaim,, C. P. Gallagher,, J. L. Gray,, X. E. Hu,, N. K. Kim,, H. D. MeKeever,, C. J. Miley,, T. L. Twinem,, and S. X. Zheng. 1999. Novel non-fluoroquinolones (NFQ's), structure-activity, and design of new, potent and safe agents, abstr. F-544. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
66. Ledoussal, B.,, D. Bouzard,, and E. Coroneos. 1992. Potent non-6-fluoro-substituted quinolone antibacterials: synthesis and biological activity.J. Med. Chem. 35:198200.
67. Lee, K. W.,, S. Y. Kwon,, S. Hwang,, J.-U. Lee,, and H. Kim. 1996. Quantitative structure-activity relationships (QSAR) study on C-7 substituted quinolone. Bull. Kor. Chem. Soc. 17:147152.
68. Li, Q.,, D. T. W. Chu,, A. Claiborne,, C. S. Cooper,, C. M. Lee,, K. Raye,, K. B. Berst,, P. Donner,, W. Wang,, L. Hasvold,, A. Fung,, Z. Ma,, M. Tufano,, R. Flamm,, L. L. Shen,, J. Baranowski,, A. Nilius,, J. Alder,, J. Meulbroek,, K. Marsh,, D. Crowell,, Y. Hui,, L. Seif,, L. M. Melcher,, R. Henry,, S. Spanton,, R. Faghih,, L. L. Klein,, S. Ken Tanaka,, and J. J. Plattner. 1996. Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents. J. Med. Chem. 39:30703088.
69. Li, Q.,, L. A. Mitscher,, and L. L. Shen. 2000. The 2-pyridone antibacterial agents: bacterial topoisomerase inhibitors. Med. Res. Rev. 20:231293.
70. Lietman, P. S. 1995. Fluoroquinolone toxicities: An update. Drugs 49(Suppl. 2):159163.
71. Lode, H. 1999. Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Safety 21:123135.
72. Lohray, B. B.,, S. Baskaran,, B. S. Rao,, B. Mallesham,, K. S. N. Bharath,, B. Y. Reddy,, S. Venkateswarlu,, A. K. Sadhukhan,, M. S. Kumar,, and H. M. Sarnaik. 1998. Novel quinolone derivatives as potent antibacterials. Bioorg. Med. Chem. Lett. 8:525528.
73. Lowe, M. N.,, and H. M. Lamb. May 2000. Gemifloxacin. Drugs 59:11371147.
74. Mallalieu, N. L.,, D. H. Ellis,, P. H. Zoutendam,, M. Gavin,, M. K. Dirr,, M. Martin,, and B. Ledoussal. 1999. Preclinical pharmacokinetics of non-fluoroquinolone antibacterials, abstr. F-550. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
75. Martel, A. M.,, P. A. Leeson,, and J. Castaner. 1997. Moxifloxacin. Drugs Future 22:109113.
76. Mirzaei, M.,, and A. Foroumadi. 2000. Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with a 2-thienyl group. Pharm. Pharmacol. Commun. 6:351354.
77. Moran, D. B.,, C. B. Ziegler, Jr.,, T. S. Dunne,, N. A. Kuck,, and Y. I. Lin. 1989. Synthesis of novel 5-fluoro analogues of norfloxacin and ciprofloxacin. J. Med. Chem. 32:13131318.
78. Murphy, V.,, J. Hannah-Hardy,, H. Murli,, H. Raabe,, G. Douds,, K. Sealover,, P. Young,, E. Swing,, N. Nikolaides,, S. Mundla,, M. Reilly,, and T. Schunk. 1999. Preliminary toxicity of a series of non-fluoroquinolones (NFQ's), abstr. F-554. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
79. Nagai, A.,, M. Takahata,, M. Miyazaki,, Y. Kawamura,, T. Kodama,, Y. Todo,, Y. Watanabe,, and H. Narita. 1997. T-3811, a novel des-F(6)-quinolone: toxicological evaluation, abstr. F-162. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
80. Nam, K.-S.,, B.-J. Kim,, T.-S. Lee,, and W.-J. Kin. 1996. New quinolone antibacterial agents introducing new functional groups at C-3 position. Kor. J. Med. Chem. 6:203238.
81. Nieto, M. J.,, F. Alovero,, R. H. Manzo,, and M. R. Mazzieri. 1999. A new class of fluoroquinolones: benzenesulfonamidefluoroquinolones (BSFQs), antibacterial activity and SAR studies. Eur. J. Med. Chem. 34:209214.
82. Park, K. H.,, I. H. Cho,, J. M. Lee,, J. A. Kang,, Y. G. Kim,, K. H. Hong,, J. H. Kim,, and T. Nishino. 1995. In vitro and in vivo antibacterial activities of CFC-222, a novel broad spectrum fluoroquinolone. Drugs 49(Suppl. 2):240242.
83. Park, T.-H.,, K.-S. Nam,, Y.-H. Ha,, Y.-J. Choi,, J.-D. Ha,, J.-Y. King,, and Y.-H. Kim. 1997. Synthesis and antibacterial activity of KRQ-10018 and its analogues: potent DNA gyrase inhibitors, abstr. F-173. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
84. Pavan, B.,, and F. Vesce. 1999. Sitafloxacin. Curr. Opin. Anti-Infect. Investig. Drugs 1:478487.
85. Reuman, M.,, S. J. Daum,, B. Singh,, M. P. Wentland,, R. B. Perni,, P. Pennock,, P. M. Carabateas,, M. D. Gruett,, M. T. Saindane,, P. H. Dorff,, S. A. Coughlin,, D. M. Sedlock,, J. B. Rake,, and G. Y. Lesher. 1995. Synthesis and antibacterial activity of some novel 1-substituted 1,4 dihydro-4-oxo-7- pyridinyl-3-quinolinecarboxylic acids. Potent antistaphylococcal agents.J. Med. Chem. 38:25312540.
86. Ryan, B.,, H.-T. Ho,, P. Wu,, M.-B. Frosco,, T. Dougherty,, and J. F. Barrett. 2000. 40th Interscience Conference on antimicrobial agents and chemotherapy (ICAAC). Exp. Opin. Investig. Drugs 9:29452972.
87. Sabatini, S.,, V. Cecchetti,, O. Tabarrini,, and A. Fravolini. 1999. 8-Methyl-7-substituted-l, 6-napthyridine-3-carboxylic acids as new 6-desfluoroquinolone antibacterials [1].J. Heterocycl. Chem. 36:953957.
88. Sahm, D. F.,, A. M. Staples,, I. A. Critchley,, C. Thornsberry,, K. S. Murfitt,, J. A. Karlowsky,, and D. C. Mayfield. 2000. Activities of non-fluorinated quinolones against recent clinical isolates of gram-positive cocci, including those resistant to currently available fluoroquinolones, abstr. 1509. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
89. Sakurai, N.,, F. Hirayama,, M. Sano,, S. Uemori,, A. Moriguchi,, Y. Yokoyama,, K. Yamamoto,, M. Miyoshi,, Y. Ikeda,, and T. Kawakita. 1998. Synthesis and anti- Helicobacter pylori activity of Y-34867, a new 7-morpholinoquinolone, abstr. F-085. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
90. Sakurai, N.,, M. Sano,, F. Hirayama,, T. Kuroda,, S. Uemori,, A. Moriguchi,, K. Yamamoto,, Y. Ikeda,, and T. Kawakita. 1998. Synthesis and structure-activity relationships of 7-(2-aminoalkyl)morpholinoquinolones as anti-Helicobacter pylori agents. Bioorg. Med. Chem. Lett. 8:21852190.
91. Sanchez, J. P.,, R. D. Gogliotti,, J. M. Domagala,, S. J. Gracheck,, M. D. Huband,, J. A. Sesnie,, M. A. Cohen,, and M. A. Shapiro. 1995. The synthesis, structure-activity, and structure-side effect relationships of a series of 8-alkoxyand 5-amino-8-alkoxyquinolone antibacterial agents.J. Med. Chem. 38:44784487.
92. Schultz, C. C.,, Y. Nan,, T. Marron,, A. Nilius,, M. Bui,, P. Raney,, G. Stone,, L. Shen,, J. Baranowski,, R. Snyder,, and Y. S. Or. 1999. Synthesis and antibacterial activity of C-8 carbon linked 2-pyridones, Abstr. F-560. In Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
93. Segawa, J.,, K. Kazuno,, M. Matsuoka,, I. Amimoto,, M. Ozaki,, M. Matsuda,, Y. Tomii,, M. Kitano,, and M. Kise. 1995. Studies of pyridonecarboxylic acids. IV. Synthesis and antibacterial activity evaluation of S-(2)- and R-(1 )-6-fluorol- methyl-4-oxo-7-(l-piperazinyl)-4H-[l,3]thiazeto[3, 2- a]quinoline-3-carboxylic acids. Chem. Pharm. Bull. 43:12381240.
94. Shapiro, M. A.,, J. A. Dever,, T. Joannides,, J. A. Sesnie,, and S. Vanderroest. 1995. In vivo therapeutic efficacies of PD 138312 and PD 140248, two novel fluoronaphthyridines with outstanding gram-positive potency. Antimicrob. Agents Chemother. 39:21832186.
95. Sheu, J. Y.,, Y. L. Chen,, K. C. Fang,, T. C. Wang,, C. H. Peng,, and C. C. Tzeng. 1998. Synthesis and antibacterial activity of l-(substituted-benzyl)-6-fluoro-l,4-dihydro-4-oxoquinoline- 3-carboxylic acids and their 6,8-difluoro analogs. J. Heterocycl. Chem. 35:955964.
96. Singh, R.,, R. Fathi-Afshar,, G. Thomas,, M. P. Singh,, F. Higashitani,, A. Hyodo,, N. Unemi,, and R. G. Micetich. 1998. Synthesis and antibacterial activity of 7-hydrazinoquinolones. Eur. J. Med. Chem. 33:697703.
97. Suto, M. J.,, J. M. Domagala,, G. E. Roland,, G. B. Mailloux,, and M. A. Cohen. 1992. Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity. J. Med. Chem. 35:47454750.
98. Takahashi, H.,, K. Kawakami,, K. Sugita,, H. Ohki,, K. Kimura,, S. Miyauchi,, H. Inagaki,, R. Miyauchi,, M. Tanaka,, M. Chiba,, E. Yamazaki,, K. Sato,, Y. Kurosaka,, S. Nishida,, Y. Murakami,, T. Otani,, K. Yabe,, N. Haga,, T. Jindo,, K. Takasuna,, F. Yamaguchi,, M. Sekiguchi,, I. Hayakawa,, and M. Takemura. 2000. Synthesis and biological evaluation of D61-1113, a novel fluoroquinolone having potent activity against gram-positive bacteria including MRSA, PRSP, and VRE, abstr. F-1505. In Proceedings of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C..
99. Takahashi, H.,, K. Kawakami,, K. Sugita,, H. Ohki,, K. Kimura,, R. Miyauchi,, K. Sato,, and M. Takemura. 1998. DC-756: A new methoxyquinolone: synthesis and in vitro activity of 7-[(3-amino-4-substituted)pyrroldin-l-yl] derivatives, abstr. F-73. In Proceedings of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C..
100. Takahashi, Y.,, N. Masuda,, M. Otsuki,, M. Miki,, and T. Nishino. 1997. In vitro activity of HSR-903, a new quinolone. Antimicrob. Agents Chemother. 41:13261330.
101. Takahata, M.,, J. Mitsuyama,, Y. Yamashiro,, H. Araki,, H. Yamada,, H. Hayakawa,, Y. Todo,, S. Minami,, Y. Watanabe,, and H. Narita. 1997. T-3811, a novel des-F(6)-quinolone: study of pharmacokinetics in animals, abstr. F-160. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C..
102. Takahata, M.,, J. Mitsuyama,, Y. Yamashiro,, M. Yonezawa,, H. Araki,, Y. Todo,, S. Minami,, Y. Watanabe,, and N. Hirokazu. 1999. In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. Antimicrob. Agents Chemother. 43:10771084.
103. Todo, Y.,, J. Nitta,, M. Miyajima,, Y. Fukuoka,, Y. Yamashiro,, N. Nishida,, I. Saikawa,, and H. Narita. 1994. Pyridonecarboxylic acids as antibacterial agents. VIII. Synthesis and structure-activity relationship of 7-(laminocyclopropyl)- 4-oxo-l,8-naphthyridine-3-carboxylic acids and 7-(l-aminocyclopropyl)-4-oxoquinolone-3-carboxylic acids. Chem. Pharm. Bull. 42:20632070.
104. Todo, Y.,, H. Takagi,, F. lino,, Y. Fukuoka,, Y. Ikeda,, K. Tanaka,, I. Saikawa,, and H. Narita. 1994. Pyridonecarboxylic acids as antibacterial agents. VI. Synthesis and structure-activity relationship of 7-(alkyl, cycloalkyl, and vinyl)-l-cyclopropyl-6-fluoro-4-quinolone- 3-carboxylic acids. Chem. Pharm. Bull. 42:20492054.
105. Todo, Y.,, H. Takagi,, F. lino,, Y. Fukuoka,, M. Takahata,, S. Okamoto,, I. Saikawa,, and H. Narita. 1994. Pyridonecarboxylic acids as antibacterial agents. DC. Synthesis and structure-activity relationship of 3-substituted 10-(1- aminocyclopropyl)-9-fluoro-7-oxo-2,3-dihydro-7H-pyrido[ l,2,3-<i/e]-l,4-benzoxazine-6-carboxylic acids and their 1- thio and 1-aza analogues. Chem. Pharm. Bull. 42:25692574.
106. Tomioka, H.,, K. Sato,, H. Kajitani,, T. Akaki,, and S. Shishido. 2000. Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Antimicrob. Agents Chemother. 44:283286.
107. Wentland, M. P.,, G. Y. Lesher,, M. Reuman,, M. D. Gruett,, B. Singh,, S. C. Aldous,, P. H. Dorff,, J. B. Rake,, and S. A. Coughlin. 1993. Mammalian topoisomerase II inhibitory activity of l-cyclopropyl-6,8-difluoro-l,4-dihydro-7-(2,6- dimethyl-l-4-pyridinyl)-4-ox o-3-quinolinecarboxylic acid and related derivatives. J. Med. Chem. 36:28012809.
108. Wise, R.,, P. G. Pagella,, V. Cecchetti,, A. Fravolini,, and O. Tabarrini. 1995. In vitro activity of MF 5137, a new potent 6-aminoqionolone. Drugs. 49(Suppl. 2):272273.
109. Yamada, H.,, H. Hisada,, J. Mitsuyama,, M. Takahata,, Y. Todo,, S. Minami,, N. Terashima,, Y. Wantanabe,, and H. Narita. 2000. BMS-284756 (T-3811ME), a des-fluoro(6)- quinolone. Selectivity between bacterial and human type II DNA topoisomerases, abstr. C-753. In Proceedings of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C..
110. Yoon, S. J.,, Y. H. Chung,, C. H. Lee,, Y. S. Oh,, D. R. Choi,, N. D. Kim,, J. K. Lim,, Y. H. Jin,, D. K. Lee,, and W. Y. Lee. 1997. Synthesis, pharmacokinetics, and biological activity of a series of new pyridonecarboxylic acid antibacterial agents bearing a 5-fluoro-2-pyridyl group or a 3-fluoro-4-pyridyl group at N - l J. Heterocycl. Chem. 34:10211026.
111. Yoshida, T.,, Y. Yamamoto,, H. Orita,, M. Kakiuchi,, Y. Takahashi,, M. Itakura,, N. Kado,, K. Mitani,, S. Yasuda,, H. Kato,, and Y. Itoh. 1996. Structure-activity relationships of antibacterial activity and side effects for 5- or 8- substituted and 5,8-disubstituted-7-(3-amino-l-pyrrolidinyl)-l-cyclopropyl- 1, 4-dihydro-4-oxoquinoline-3-carboxylic acids. Chem. Pharm. Bull. 44:10741085.
112. Yoshido, T.,, Y. Yamamoto,, H. Orita,, M. Kakiuchi,, Y. Takahashi,, M. Itakura,, N. Kado,, K. Mitani,, S. Yasuda,, H. Kato,, and Y. Itoh. 1996. Studies on quinolone anibacterials. IV. Structure-activity relationships of antibacterial activity and side effects for 5- or 8-substituted and 5,8-disubstituted- 7-(3-amino-l-pyrroldinyl)-l-cyclopropyl-l,4-dihydro-4-oxo quinoline-3-carboxylic acids. Chem. Pharm. Bull. 44: 10741085.

Tables

Generic image for table
Table 1

MICs of structures 11 and 12

Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
Generic image for table
Table 2

MICs and gyrase inhibition of compound 30

Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1
Generic image for table
Table 3

Effect of a fluorine at position 6 on genotoxicity

Citation: Domagala J, Hagen S. 2003. Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not, p 3-18. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch1

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