Quinolone Antibiotics: The Development of Moxifloxacin

Analogue-based Drug Discovery

Volumn , Issue , 2006, Pages 315-370

  Petersen, Uwe ^a  

^a NONE

Author keywords

Analogue based drug discovery; Chemical evolution; Development of Moxifloxacin; Development of resistance; Excretion and biodegradability of Moxifloxacin; Metabolism; Microbiological and clinical properties; Pharmacokinetics pharmacodynamics; Physicochemical properties; Quinolone antibiotics; Safety and tolerability; Synthetic routes

Indexed keywords

EID: 62549107911     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/3527608001.ch17     Document Type: Chapter

References (287)

1. Lesher GY, et al.1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J. Med. Pharm. Chem., 1962, 91, 1063-1065.
2. Bozdogan B, Appelbaum PC.Oxazolidinones: activity, mode of action, and mechanism of resistance. Int. J. Antimicrob. Agents, 2004, 23, 113-119.
3. Li Q, Mitscher LA, Shen LL.The 2-pyridone antibacterial agents: bacterial topoisomerase inhibitors. Med. Res. Rev., 2000, 20, 231-293.
4. Takahata M, et al.In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. Antimicrob. Agents Chemother., 1999, 43, 1077-1084.
5. Roca J.The mechanisms of DNA topoisomerases. Trends Biochem. Sci., 1995, 20, 156-160.
6. Drlica K, Zhao X.DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev., 1997, 61, 377-392.
7. Maxwell A, Critchlow SE.Mode of action. In: Quinolone Antibacterials. Kuhlmann J, Dalhoff A, Zeiler H-J (Eds.) Springer: Berlin, Heidelberg, New York, Barcelona, Budapest, Hong Kong, London, Milan, Paris, Santa Clara, Singapore, Tokyo, 1998, pp. 119-166.
8. Hooper DC. Mode of action of fluoroquinolones. Drugs, 1999, 58 (Suppl. 2), 6-10.
9. Drlica K.Mechanism of fluoroquinolone action. Curr. Opin. Microbiol., 1999, 2, 504-508.
10. Dougherty TJ, Beaulieu D, Barrett JF.New quinolones and the impact on resistance. Drug Discov. Today, 2001, 6, 529-536.
11. Heisig P, Wiedemann B.Actio und Reactio-Wirkungs-und Resistenzmechanismen der Chinolone. Pharm i u Zeit, 2001, 30, 382-393.
12. Zhanel GG, et al.A critical review of the fluoroquinolones: focus on respiratory infections. Drugs, 2002, 62, 13-59.
13. ICI: BE 564 863, 1954.
14. Kaminsky D, Meltzer RJ.Quinolone antibacterial agents. Oxolinic acid and related compounds. J. Med. Chem., 1968, 11, 160-163.
15. Scavone JM, Gleckman RA, Fraser DG.Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. Pharmacotherapy, 1982, 2, 266-272.
16. Minami S, Shono T, Matsumoto J.Pyrido[2,3-d]pyrimidine antibacterial agents. II. Piromidic acid and related compounds. Chem. Pharm. Bull., 1971, 19, 1426.
17. Matsumoto J, Minami S.Pyrido(2,3-d)pyrimidine antibacterial agents. 3. 8-Alkyl-and 8-vinyl-5,8-dihydro-5-oxo-2-(1-piperazinyl) pyrido(2,3-d)pyrimidine-6-carboxylic acids and their derivatives. J. Med. Chem., 1975, 18, 74-79.
18. Gerster JF.1975. Minnesota Mining: US Patent 3 917 609 [C. A. 84, 30 930 (1976)].
19. Koga H, et al.Structure-activity relationships of antibacterial 6,7-and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids. J. Med. Chem., 1980, 23, 1358-1363.
20. Goueffon Y.et al. A new synthetic antibacterial: 1-ethyl-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (1589 R.B.). C. R. Seances Acad. Sci. III, 1981, 292, 37-40.
21. Matsumoto J, et al.Pyridonecarboxylic acids as antibacterial agents. 2. Synthesis and structure-activity relationships of 1,6,7-trisubstituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids, including enoxacin, a new antibacterial agent. J. Heterocycl. Chem., 1984, 27, 292-301.
22. Bremner DA, Dickie AS, Singh KP.In-vitro activity of fleroxacin compared with three other quinolones. J. Antimicrob. Chemother., 1988, 22 (Suppl. D), 19-23.
23. Grohe K, Zeiler HJ, Metzger K.1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazinoquinoline-3-carboxylic acids and an antibacterial agent containing them. 1981. Bayer AG: DE 3 142 854 [C. A. 99, 53 790 h (1983)].
24. Zeiler HJ, Grohe K.The in vitro and in vivo activity of ciprofloxacin. Eur. J. Clin. Microbiol., 1984, 3, 339-343.
25. Wise R, Andrews JM, Edwards LJ.In vitro activity of Bay O 9867, a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrob. Agents Chemother., 1983, 23, 559-564.
26. Sato K, et al.In vitro and in vivo activity of DL-8280, a new oxazine derivative. Antimicrob. Agents Chemother., 1982, 22, 548-553.
27. Hayakawa I, Hiramitsu T, Tanaka Y.Synthesis and antibacterial activities of substituted 7-oxo-2,3-dihydro-7Hpyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acids. Chem. Pharm. Bull. (Tokyo), 1984, 32, 4907-4913.
28. Atarashi S, et al.Synthesis and antibacterial activities of optically active ofloxacin and its fluoromethyl derivative. Chem. Pharm. Bull. (Tokyo), 1987, 35, 1896-1902.
29. Grohe K, Heitzer H.Synthese von 4-Chinolon-3-carbonsäuren. Liebigs Ann. Chem., 1987, 29-37.
30. Grohe K.The importance of the cycloaracylation process for the synthesis of modern fluoroquinolones. J. prakt. Chem., 1993, 335, 397-409.
31. Grohe K.The chemistry of the quinolones: Methods of synthesizing the quinolone ring system. In: Quinolone Antibacterials. Kuhlmann J, Dalhoff A, Zeiler H-J (Eds.) Springer: Berlin, Heidelberg, New York, Barcelona, Budapest, Hong Kong, London, Milan, Paris, Santa Clara, Singapore, Tokyo, 1998, pp. 13-62.
32. Petersen U, Schenke T.The chemistry of the quinolones: Chemistry in the periphery of the quinolones. In: Quinolone Antibacterials. Kuhlmann J, Dalhoff A, Zeiler H-J (Eds.) Springer: Berlin, Heidelberg, New York, Barcelona, Budapest, Hong Kong, London, Milan, Paris, Santa Clara, Singapore, Tokyo, 1998, pp. 63-118.
33. Dalhoff A, Petersen U, Endermann R.In vitro activity of BAY 12-8039, a new 8-methoxyquinolone. Chemotherapy (Basel), 1996, 42, 410-425.
34. Petersen U, et al.The synthesis and in vitro and in vivo antibacterial activity of moxifloxacin (BAY 12-8039), a new 8-methoxyquinolone. In: Moxifloxacin in practice, Vol. 1. Adam D, Finch R (Eds.) Maxim Medical: Oxford, 1999, pp. 13-26.
35. Bay 12-8039, Moxifloxacin hydrochloride.Drugs Fut., 1999, 24, 193-197.
36. Moxifloxacin hydrochloride, Bay 12-8039, Avelox®, Avalox®, Actira®, Octegra®, Proflox®.Drugs Fut., 2000, 25, 211-219.
37. Moxifloxacin hydrochloride, Avelox®, Avalox®, Actira®, Octegra®, Proflox®.Drugs Fut., 2001, 26, 189-194.
38. Hosaka M, et al.In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy-quinolone. Antimicrob. Agents Chemother., 1992, 36, 2108-2117.
39. AM 1155.Drugs Fut., 1993, 18, 203-205.
40. AM-1155.Drugs Fut., 1994, 19, 280-281.
41. AM-1155.Drugs Fut., 1995, 20, 293.
42. Perry CM, et al.Gatifloxacin: a review of its use in the management of bacterial infections. Drugs, 2002, 62, 169-207.
43. Gatifloxacin, Tequin®, Gatiflo®.Drugs Fut., 2000, 25, 311-317.
44. Gatifloxacin, Tequin®, Gatiflo®.Drugs Fut., 2001, 26, 297-301.
45. Naber KG, Adam D.Classification of fluoroquinolones. Int. J. Antimicrob. Agents, 1998, 10, 255-257.
46. King DE, Malone R, Lilley SH.New classification and update on the quinolone antibiotics. Am. Fam. Physician, 2000, 61, 2741-2748.
47. Albrecht R.Development of antibacterial agents of the nalidixic acid type. In: Progress in Drug Research-Fortschritte der Arzneimittelforschung, Vol. 21. Jucker E (Ed.) Birkhäuser: Basel, Stuttgart, 1977, pp. 9-104.
48. Bouzard D.Recent advances in the chemistry of quinolones. In: Recent Progress in the Chemical Synthesis of Antibiotics. Lukacs G (Ed.) Springer-Verlag, Berlin, Heidelberg, 1990, pp. 249-283.
49. Chu DTW.Fluoroquinolone carboxylic acids as antibacterial drugs. In: Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications. Filler R, Kobayashi Y, and Yagupolskii LM (Eds.). Elsevier: Amsterdam, London, New York, Tokyo, 1993, pp. 165-207.
50. Chu DTW, Fernandes PB.Recent developments in the field of quinolone antibacterial agents. Adv. Drug Res., 1991, 21, 39-144.
51. Lesher GY.Nalidixic acid and other quinolone carboxylic acids. In: Encyclopedia of Chemical Technology, 3rd edn. Kirk-Othmer (Ed.) John Wiley & Sons: New York, Chichester, Brisbane, Toronto, 1978, pp. 782-789.
52. Leysen DC, et al.Synthesis of antibacterial 4-quinolone-3-carboxylic acids and their derivatives. Part 1. Pharmazie, 1991, 46, 485-501.
53. Leysen DC, et al.Synthesis of antibacterial 4-quinolone-3-carboxylic acids and their derivatives. Part 2. Pharmazie, 1991, 46, 557-572.
54. Mitscher LA, et al.Recent advances on quinolone antimicrobial agents. In: Horizons on Antibiotic Research. Davis BD, et al. (Eds.) Japan Antibiotics Research Association: Tokyo, 1988, pp. 166-193.
55. Rádl S, Bouzard D.Recent advances in the synthesis of antibacterial quinolones. Heterocycles, 1992, 34, 2143-2177.
56. Mitscher LA.Bacterial topoisomerase inhibitors: quinolone and pyridone antibacterial agents. Chem. Rev., 2005, 105, 559-592.
57. Andriole VT.The Quinolones. Academic Press: London, San Diego, New York, Berkeley, Boston, Sydney, Tokyo, Toronto, 1988.
58. Asahina Y, Ishizaki T, Suzue S.Recent advances in structure activity relationships in new quinolones. In: Fluorinated quinolones-new quinolone antimicrobials; Progress in Dug Research-Fortschritte der Arzneimittelforschung. Jucker E (Ed.), Vol. 38. Mitsuhashi (Ed.) Birkhäuser: Basel Stuttgart, 1992, pp. 57-106.
59. Domagala JM.Review: Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J. Antimicrob. Chemother., 1994, 33, 685-706.
60. Mitscher LA, Devasthale PV, Zavod RM.Structure-activity relationships of fluoro-4-quinolones. In: The 4-Quinolones: Antibacterial Agents in Vitro. Crumplin GC (Ed.). Springer: London, Berlin, Heidelberg, New York, Paris, Tokyo, Hong Kong, 1990, pp. 115-146.
61. Mitscher LA, Devasthale P, Zavod R.Structure-activity relationships. In: Quinolone Antimicrobials Agents, 2nd edn. Hooper DC, Wolfson JS (Eds.) American Society for Microbiology: Washington, 1993, pp. 3-51.
62. Rádl S.Structure-activity relationships in DNA gyrase inhibitors. Pharmacol. Ther., 1990, 48, 1-17.
63. Rosen T.The fluoroquinolone antibacterial agents. In: Progress in Medicinal Chemistry, Vol. 27. Ellis GP, West GB (Eds.). Elsevier: Amsterdam, New York, Oxford, 1990, pp. 235-295.
64. Schentag JJ, Domagala JM.Structure-activity relationships with the quinolone antibiotics. Res. Clin. Forums, 1985, 7, 9-13.
65. Gootz TD, Brighty KE.Fluoroquinolone antibacterials: SAR mechanism of action, resistance, and clinical aspects. Med. Res. Rev., 1996, 16, 433-486.
66. Domagala J, Hagen SE.Structure-activity relationships of the quinolone antibacterials in the new millennium: Some things change and some do not. In: Quinolone Antimicrobial Agents. Hooper DC, Rubinstein E (Eds.) ASM Press: Washington, DC, 2003, pp. 3-18.
67. Schmitz FJ, et al.Activity of quinolones against gram-positive cocci: mechanisms of drug action and bacterial resistance. Eur. J. Clin. Microbiol. Infect. Dis., 2002, 21, 647-659.
68. Bertino JJ, Fish D.The safety profile of the fluoroquinolones. Clin. Ther., 2000, 22, 798-817.
69. Rubinstein E.History of quinolones and their side effects. Chemotherapy, 2001, 47 (Suppl. 3), 3-8.
70. Petersen U, et al.7-Amino-1-cyclopropyl-6,8-dihalogen-1,4-dihydro-4-oxo-3-chinolincarbonsäuren, Verfahren zu ihrer Herstellung sowie diese enthaltene antibakterielle Mittel. 1984. Bayer AG: EP 167 763 [C.A. 104: 186 447v].
71. Irikura T, et al.Quinolonecarboxylic acid derivative and process for its preparation. 1985. Kyorin Pharmaceutical Co: EP 195 316 [C.A.: 106, 50068f].
72. AM-1091, Clinafloxacin, PD-127391, Bay-V 3545, CI-960. Drugs Fut., 1992, 17, 938-940.
73. Clinafloxacin, AM-1091, PD-127391, Bay-V 3545, CI-960 (as HCl).Drugs Fut., 1993, 18, 962.
74. Clinafloxacin.Drugs Fut., 1994, 19, 950-960.
75. Cohen MA, et al.In-vitro activity of clinafloxacin, trovafloxacin, and ciprofloxacin. J. Antimicrob. Chemother., 1997, 40(2), 205-211.
76. Clinafloxacin.Drugs Fut., 1999, 24, 1131-1134.
77. Petersen U, et al.Enantiomerenreine 7-(3-Amino-1-pyrrolidinyl)-chinolonund-naphthyridoncarbonsäuren. 1989. Bayer AG: EP 26 744.
78. Humphrey GH, et al.Pharmacokinetics of clinafloxacin enantiomers in humans. J. Clin. Pharmacol., 1999, 39, 1143-1150.
79. Benkert K, Wiegand H.Stellungnahme der Firma Gödecke Parke-Davis. Chemother. J., 2000, 9, 100-101.
80. Prous J, Graul A, Castañer J.DU-6859. Drugs Fut., 1994, 19, 827-834.
81. DU-6859, Sitafloxacin.Drugs Fut., 1997, 22, 1035ff.
82. Sitafloxacin, DU-6859.Drugs Fut., 1998, 23, 1047.
83. Sitafloxacin hydrate, DU-6859 a.Drugs Fut., 1999, 24, 1040-1042.
84. Sitafloxacin hydrate.Drugs Fut., 2000, 25, 993-995.
85. Kawakami K, et al.DK-507k, a New 8-Methoxyquinolone: Synthesis and Biological Evaluation of 7-[(3-amino-4-substituted) pyrrolidin-1-yl] Derivatives. In: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract F-546. Chicago, 2001.
86. Otani T, et al.DK-507k, a New 8-Methoxyquinolone: In Vitro and In Vivo Antibacterial Activities. In: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract F-547. Chicago, 2001.
87. Takahashi Y, et al.In vitro activity of HSR-903, a new quinolone. Antimicrob. Agents Chemother., 1997, 41, 1326-1330.
88. Yoshizumi S, et al.In vivo activity of HSR-903, a new fluoroquinolone, against respiratory pathogens. Antimicrob. Agents Chemother., 1998, 42, 785-788.
89. Yoshizumi S, et al.The in vivo activity of olamufloxacin (HSR-903) in systemic and urinary tract infections in mice. J. Antimicrob. Chemother., 2001, 48, 137-140.
90. Sun J, et al.Protonation equilibrium and lipophilicity of olamufloxacin (HSR-903), a newly synthesized fluoroquinolone antibacterial. Eur. J. Pharm. Biopharm., 2003, 56, 223-229.
91. Domagala JM, et al.1-Ethyl-7-[3-[(ethylamino) methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid. New quinolone antibacterial with potent gram-positive activity. J. Med. Chem., 1986, 29, 445-448.
92. Brighty KE, Gootz TD.The chemistry and biological profile of trovafloxacin. J. Antimicrob. Chemother., 1997, 39 (Suppl. B), 1-14.
93. Lode H.Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Safety, 1999, 21, 123-135.
94. Hong CY, et al.Novel fluoroquinolone antibacterial agents containing oximesubstituted (aminomethyl)pyrrolidines: synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid (LB 20 304). J. Med. Chem., 1997, 40, 3584-3593.
95. SB-265805/LB-20304a, Gemifloxacin mesilate. Drugs Fut., 1999, 24, 1281-1286.
96. Gemifloxacin mesilate, SB-265805/ LB-20304a, Factive®. Drugs Fut., 2000, 25, 1194-1202.
97. Blondeau JM, Missaghi B.Gemifloxacin: a new fluoroquinolone. Expert Opin. Pharmacother., 2004, 5, 1117-1152.
98. Hong CY.Discovery of gemifloxacin (Factive, LB20304a): a quinolone of a new generation. Farmaco,2001, 56, 41-44.
99. Saravolatz LD, Leggett J.Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones.Clin. Infect. Dis., 2003, 37, 1210-1215.
100. Yun HJ, et al.In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic.Antimicrob. Agents Chemother., 2002, 46, 3071-3074.
101. Birkofer L, Feldmann H.Über bicyclische Dilactame.Liebigs Ann. Chem., 1964, 677, 154-157.
102. Schenke T, Petersen U.Diazabicyclo[3.3.0]octane und ein Verfahren zu ihrer Herstellung.1989. Bayer AG: EP 393 424.
103. Petersen U, et al.7-(1-Pyrrolidinyl)-3-chinolon-und naphthyridoncarbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie substituierte mono-und bicyclische Pyrrolidinderivate als Zwischenprodukte zu ihrer Herstellung und sie enthaltende antibakterielle Mittel und Futterzusatzstoffe.1988/1989. Bayer AG: EP 350 733.
104. Petersen U, et al.7-(2,7-Diazabicyclo[3.3.0]octyl)-3-chinolon-und naphthyridoncarbonsäure-Derivate.1990. Bayer AG: EP 481 274.
105. Laborde E, Schroeder M.7-Substituted quinolones and naphthyridones as antibacterial agents. 1992. Warner-Lambert Co.: US 5 342 844.
106. Kitzis MD, et al.SYN987, SYN1193, and SYN1253, new quinolones highly active against gram-positive cocci. J. Antimicrob. Chemother., 1995, 36, 209-213.
107. Klopman G, et al.Anti-Mycobacterium avium activity of quinolones: in vitro activities. Antimicrob. Agents Chemother., 1993, 37, 1799-1806.
108. Petersen U, et al.Quinolone-and naphthyridone carboxylic acid derivatives, process for their production, antibacterial compositions and feed additives containing them. 1988. Bayer AG: US 5 173 484.
109. Ogata M, et al.Synthesis and antibacterial activity of new 7-(aminoazabicycloalkanyl) quinolonecarboxylic acids. Eur. J. Med. Chem., 1991, 26, 889-906.
110. Petersen U, et al.7-(Aminomethyl-oxa-7-aza-bicyclo[3.3.0]oct-7-yl)-chinolonund naphthyridoncarbonsäure-Derivate. 1992. Bayer AG: EP 589 318.
111. Petersen U, et al.Quinolone-and naphthyridonecarboxylic acid derivatives. 1994. Bayer AG: EP 705 828.
112. Dimpfel W, et al.Hippocampal activity in the presence of quinolones and fenbufen in vitro. Antimicrob. Agents Chemother., 1991, 35, 1142-1146.
113. Schmuck G, Schürmann A, Schlüter G.Determination of the excitatory potencies of fluoroquinolones in the central nervous system by an in vitro model. Antimicrob. Agents Chemother., 1998, 42, 1831-1836.
114. Petersen U, et al.Verwendung von 7-(1-Aminomethyl-2-oxa-7-aza-bicyclo[3.3.0]oct-7-yl)-chinoloncarbonsäureund-naphthyridoncarbonsäure-Derivaten zur Therapie von Helicobacter pylori-Infektionen und den damit assoziierten gastroduodenalen Erkrankungen. 1996. Bayer AG: DE 19 652 219.
115. Matzke M, et al.Verwendung von 7-(2-Oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-chinoloncarbonsäure-und-naphthyridoncarbonsäure-Derivaten zur Therapie von Helicobacter pylori-Infektionen und den damit assoziierten gastroduodenalen Erkrankungen. 1996. Bayer AG: DE 19 652 239.
116. Kim JH, et al.In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone. Antimicrob. Agents Chemother., 1997, 41, 2209-2213.
117. Kim JH, et al.In-vitro and in-vivo antibacterial activity of CFC-222, a new fluoroquinolone. J. Antimicrob. Chemother., 1998, 41, 223-229.
118. Yatsunami T, et al.Isoindoline derivative. 1988. Wakunaga Seiyaku Kabushiki Kaisha: EP 343 560.
119. Petersen U, et al.7-Azaisoindolenyl-chinolon-und naphthyridoncarbonsäure-Derivate. 1991. Bayer AG: EP 520 277.
120. Petersen U, et al.1-(2-Fluorcyclopropyl)-chinolon-und naphthyridoncarbonsäure-Derivate. 1993. Bayer AG: EP 653 425.
121. Petersen U, et al.7-Isoindolinyl-chinolon-und naphthyridoncarbonsäure-Derivate. 1991. Bayer AG: DE 4 120 646.
122. Okura A, et al.Pyridonecarboxylic acid derivative. 1990. Banyu Pharmaceutical Co.: WO92/12146.
123. Petersen U, et al.Chinolon-und Naphthyridoncarbonsäure-Derivate. 1995. Bayer AG: EP 721 948.
124. Petersen U, et al.Chinolon-und Naphthyridoncarbonsäure-Derivate. 1995. Bayer AG: EP 704 443.
125. Philipps T, et al.7-Isoindolenyl-quinolone derivatives and 7-isoindolenylnaphthyridone derivatives. 1996. Bayer AG: US 5 739 339.
126. Schenke T, Krebs A, Petersen U.Enantiomerenreine 2-Oxa-5,8-diazabicyclo[4.3.0]nonane sowie Verfahren zu ihrer Herstellung. 1992. Bayer AG: DE 4 200 415.
127. Petersen U, et al.The synthesis and biological properties of 6-fluoro-quinolonecarboxylic acids. Bull. Chim. Soc. Belg., 1996, 105, 683-699.
128. Kim WJ, et al.Novel quinolone carboxylic acid derivatives and process for preparing the same. 1994. Korea Res. Inst. Chem. Technology: EP 622 367.
129. Petersen U, et al.Chinolon-und Naphthyridoncarbonsäure-Derivate als antibakterielle Mittel. 1992. Bayer AG: EP 550 903.
130. Bremm KD, et al.In vitro evaluation of BAY Y3118, a new full-spectrum fluoroquinolone. Chemotherapy, 1992, 38, 376-387.
131. Wise R, Andrews JM, Brenwald N.The in-vitro activity of Bay y 3118, a new chlorofluoroquinolone. J. Antimicrob. Chemother., 1993, 31, 73-80.
132. Garcia-Rodriguez JA, et al.In vitro activity of BAY y 3118, and nine other antimicrobial agents against anaerobic bacteria. J. Chemother., 1995, 7, 189-196.
133. Aldridge KE.Increased activity of a new chlorofluoroquinolone, BAY y 3118, compared with activities of ciprofloxacin, sparfloxacin, and other antimicrobial agents against anaerobic bacteria. Antimicrob. Agents Chemother., 1994, 38, 1671-1674.
134. Fass RJ.In vitro activity of Bay y 3118, a new quinolone. Antimicrob. Agents Chemother., 1993, 37, 2348-2357.
135. Bauernfeind A.Comparative in-vitro activities of the new quinolone, Bay y 3118, and ciprofloxacin, sparfloxacin, tosufloxacin, CI-960 and CI-990. J. Antimicrob. Chemother., 1993, 31, 505-522.
136. Sirgel F, Venter A, Heilmann HD.Comparative in-vitro activity of Bay y 3118, a new quinolone, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. J. Antimicrob. Chemother., 1995, 35, 349-351.
137. Schmidt U, Schlüter G.Studies on the mechanism of phototoxicity of BAY y 3118 and other quinolones. Adv. Exp. Med. Biol., 1996, 387, 117-120.
138. Petersen U, et al.BAY Y 3118, a novel 4-quinolone: Synthesis and in vitro activity. In: 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 642. Anaheim, 1992.
139. Petersen U, et al.Synthesis and in vitro activity of BAY 12-8039, a new methoxyquinolone. In: 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. F1. New Orleans, 1996.
140. Fey P.Verfahren zur Herstellung von (S,S)-Benzyl-2,8-diazabicyclo[4.3.0]nonan. 1999, Bayer AG: DE 19 821 039.
141. Dreisbach, C., Verfahren zur Racematspaltung von cis-und trans-Pyrrolopiperidin.1997, Bayer AG: DE 19 735 198.
142. Grohe, K., et al., 7-Amino-1-cyclopropyl-6,8-difluor-1,4-dihydro-4-oxo-3-chinolincarbonsäuren, Verfahren zu ihrer Herstellung sowie diese enthaltende antibakterielle Mittel.1983, Bayer AG: EP 126 355.
143. Masuzawa, K., et al., 8-Alkoxyquinolonecarboxylic acid and salts thereof excellent in the selective toxicity and process of preparing the same.1986, Kyorin Pharmaceutical Co.: EP 230 295.
144. Iwata, M., et al., Quinoline-3-carboxylic acid derivatives, their preparation and use.1986, Ube Industries: EP 241 206.
145. Grunenberg, A.and P. Bosché, A new crystal modification of 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]-non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid hydrochloride (CDCH), a process for its production and pharmaceutical preparations containing same. 1995, Bayer AG: DE 19 546 249; US 5 849 752.
146. Gehring, R., et al., Verfahren zur Herstellung von 8-Methoxy-chinoloncarbonsäuren.1999, Bayer AG: DE 19 751 948.
147. Müller HG.Unpublished results. Bayer AG, 1999.
148. Lister PD, Sanders CC.Pharmacodynamics of moxifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model. In: 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract A-21. San Diego, CA, 1998.
149. Woodcock JM, et al.In vitro activity of BAY 12-8039, a new fluoroquinolone. Antimicrob. Agents Chemother., 1997, 41(1), 101-106.
150. Bauernfeind A.Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin. J. Antimicrob. Chemother., 1997, 40, 639-651.
151. Brueggemann AB, Kugler KC, Doern GV.In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antimicrob. Agents Chemother., 1997, 41, 1594-1597.
152. Boswell FJ, Andrews JM, Wise R.Pharmacodynamic properties of BAY 12-8039 on gram-positive and gramnegative organisms as demonstrated by studies of time-kill kinetics and postantibiotic effect. Antimicrob. Agents Chemother., 1997, 41, 1377-1379.
153. Bébéar CM, et al.In vitro activity of BAY 12-8039, a new fluoroquinolone against mycoplasmas. Antimicrob. Agents Chemother., 1998, 42, 703-704.
154. Biedenbach DJ, et al.BAY 12-8039, a novel fluoroquinolone. Activity against important respiratory tract pathogens. Diagn. Microbiol. Infect. Dis., 1998, 32, 45-50.
155. Donati M, et al.Comparative in-vitro activity of moxifloxacin, minocycline and azithromycin against Chlamydia spp. J. Antimicrob. Chemother., 1999, 43, 825-827.
156. Ruckdeschel G, Dalhoff A.The in-vitro activity of moxifloxacin against Legionella species and the effects of medium on susceptibility test results. J. Antimicrob. Chemother., 1999, 43 (Suppl. B), 25-29.
157. Blondeau JM, Felmingham D.In vitro and in vivo activity of moxifloxacin against community respiratory tract pathogens. Clin. Drug Invest., 1999, 18, 57-78.
158. Miyashita N, et al.In-vitro activity of moxifloxacin and other fluoroquinolones against Chlamydia species. J. Infect. Chemother., 2002, 8, 115-117.
159. Goldstein EJ, et al.In vitro activity of Bay 12-8039, a new 8-methoxyquinolone, compared to the activities of 11 other oral antimicrobial agents against 390 aerobic and anaerobic bacteria isolated from human and animal bite wound skin and soft tissue infections in humans. Antimicrob. Agents Chemother., 1997, 41, 1552-1557.
160. MacGowan AP, et al.Bay 12-8039, a new 8-methoxy-quinolone: comparative in-vitro activity with nine other antimicrobials against anaerobic bacteria. J. Antimicrob. Chemother., 1997, 40, 503-509.
161. Aldridge KE, Ashcraft DS.Comparison of the in vitro activities of Bay 12-8039, a new quinolone, and other antimicrobials against clinically important anaerobes. Antimicrob. Agents Chemother., 1997, 41, 709-711.
162. Ackermann G, et al.Comparative activity of moxifloxacin in vitro against obligately anaerobic bacteria. Eur. J. Clin. Microbiol. Infect. Dis., 2000, 19, 228-232.
163. MacGowan A.Moxifloxacin (Bay 12-8039): a new methoxy quinolone antibacterial. Expert Opin. Invest. Drugs, 1999, 8, 181-199.
164. Nightingale CH.Moxifloxacin, a new antibiotic designed to treat communityacquired respiratory tract infections: a review of microbiologic and pharmacokinetic-pharmacodynamic characteristics. Pharmacotherapy, 2000, 20, 245-256.
165. Ball P.Moxifloxacin (Avelox): an 8-methoxyquinolone antibacterial with enhanced potency. Int. J. Clin. Pract., 2000, 54, 329-332.
166. Blondeau JM, Hansen GT.Moxifloxacin: a review of the microbiological, pharmacological, clinical and safety features. Expert Opin. Pharmacother., 2001, 2, 317-335.
167. Caeiro JP, Iannini PB.Moxifloxacin (Avelox): a novel fluoroquinolone with a broad spectrum of activity. Expert Rev. Anti-Infect. Ther., 2003, 1, 363-370.
168. Keating GM, Scott LJ.Moxifloxacin: a review of its use in the management of bacterial infections. Drugs, 2004, 64, 2347-2377.
169. Bartlett JG, Mundy LM.Communityacquired pneumonia. N. Engl. J. Med., 1995, 333, 1618-1624.
170. Gwaltney JMJ.Acute communityacquired sinusitis. Clin. Infect. Dis., 1996, 23, 1209-1223; quiz 1224-1225.
171. Yagupsky P, et al.In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media. Chemotherapy, 2001, 47, 354-358.
172. Ball P, Make B.Acute exacerbations of chronic bronchitis: an international comparison. Chest, 1998, 113 (3 Suppl.), 199S-204S.
173. Bartlett JG, et al.Practice guidelines for the management of communityacquired pneumonia in adults. Infectious Diseases Society of America. Clin. Infect. Dis., 2000, 31, 347-382.
174. Cubbon MD, Masterton RG.New quinolones-a fresh answer to the pneumococcus. J. Antimicrob. Chemother., 2000, 46, 869-872.
175. Esposito S, Noviello S, Ianniello F.Activity of moxifloxacin and twelve other antimicrobial agents against 216 clinical isolates of Streptococcus pneumoniae. Chemotherapy, 2001, 47, 90-96.
176. Klugman KP, Capper T.Concentrationdependent killing of antibiotic-resistant pneumococci by the methoxyquinolone moxifloxacin. J. Antimicrob. Chemother., 1997, 40, 797-802.
177. Visalli MA, Jacobs MR, Appelbaum PC.Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams. Antimicrob. Agents Chemother., 1997, 41, 2786-2789.
178. Saravolatz L, et al.Antimicrobial activity of moxifloxacin, gatifloxacin and six fluoroquinolones against Streptococcus pneumoniae. J. Antimicrob. Chemother., 2001, 47, 875-877.
179. Dalhoff A, et al.Penicillin-resistant Streptococcus pneumoniae: review of moxifloxacin activity. Clin. Infect. Dis., 2001, 32 (Suppl. 1), S22-S29.
180. Blondeau JM.A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new 'respiratory quinolones'. J. Antimicrob. Chemother., 1999, 43 (Suppl. B), 1-11.
181. Blondeau JM.Expanded activity and utility of the new fluoroquinolones: a review. Clin. Ther., 1999, 21, 3-40; discussion 1-2.
182. Fass RJ.In vitro activity of Bay 12-8039, a new 8-methoxyquinolone. Antimicrob. Agents Chemother., 1997, 41, 1818-1824.
183. Pestova E, et al.Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J. Antimicrob. Chemother., 2000, 45, 583-590.
184. Wilson R, et al.Short-term and longterm outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis. Chest, 2004, 125, 953-964.
185. Church D, et al.Efficacy of moxifloxacin in the treatment of acute bacterial sinusitis caused by penicillin-resistant Streptococcus pneumoniae. In: 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract 833. Toronto, 2000.
186. Souli M, Wennersten CB, Eliopoulos GM.In vitro activity of BAY 12-8039, a new fluoroquinolone, against species representative of respiratory tract pathogens. Int. J. Antimicrob. Agents, 1998, 10, 23-30.
187. Lemmen SW, et al.Comparison of the bactericidal activity of moxifloxacin and levofloxacin against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Klebsiella pneumoniae. Chemotherapy, 2003, 49, 33-35.
188. Aktas Z, et al.Moxifloxacin activity against clinical isolates compared with the activity of ciprofloxacin. Int. J. Antimicrob. Agents, 2002, 20, 196-200.
189. Jung R, et al.Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates. Antimicrob. Agents Chemother., 2004, 48, 1055-1057.
190. Jones ME, et al.In vitro susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a European multicenter study during 2000-2001. Clin. Microbiol. Infect., 2003, 9, 590-599.
191. Ji B, et al.In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 1998, 42, 2066-2069.
192. Rodriguez JC, et al.In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis. Int. J. Antimicrob. Agents, 2001, 17, 229-231.
193. Rodriguez JC, et al.In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis. Int. J. Antimicrob. Agents, 2002, 20, 464-467.
194. Tortoli E, Dionisio D, Fabbri C.Evaluation of moxifloxacin activity in vitro against Mycobacterium tuberculosis, including resistant and multidrug-resistant strains. J. Chemother., 2004, 14, 334-336.
195. Miyazaki E, Chaisson RE, Bishai WR.In vivo activity of BAY12-8039, a new 8-methoxy-quinolone, in a mouse model of tuberculosis. In: 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract E-210, 1998.
196. Lu T, Drlica K.In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with antituberculosis agents. J. Antimicrob. Chemother., 2003, 52, 1025-1028.
197. Rodríguez JC, et al.Mutant prevention concentration: comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis. J. Antimicrob. Chemother., 2004, 53, 441-444.
198. Nichols RL.Optimal treatment of complicated skin and skin structure infections. J. Antimicrob. Chemother., 1999, 44 (Suppl. A), 19-23.
199. Müller M, et al.Penetration of moxifloxacin into peripheral compartments in humans. Antimicrob. Agents Chemother., 1999, 43, 2345-2349.
200. Sadick NS.Systemic antibiotic agents. Dermatol. Clin., 2001, 19, 1-21.
201. Karchmer AW.Fluoroquinolone treatment of skin and skin structure infections. Drugs, 1999, 58 (Suppl. 2), 82-84.
202. Alam MR, Hershberger E, Zervos MJ.The role of fluoroquinolones in the treatment of skin and soft tissue infection. Curr. Infect. Dis. Rep., 2002, 4, 426-432.
203. Blondeau JM.The role of fluoroquinolones in skin and skin structure infections. Am. J. Clin. Dermatol., 2002, 3, 37-46.
204. Parish LC, et al.Moxifloxacin versus cephalexin in the treatment of uncomplicated skin infections. Int. J. Clin. Pract., 2000, 54, 497-503.
205. Muijsers RB, Jarvis B.Moxifloxacin in uncomplicated skin and skin structure infections. Drugs, 2002, 62, 967-973; discussion 974-975.
206. Consigny S, et al.Bactericidal activities of HMR 3647, moxifloxacin, and rifapentine against Mycobacterium leprae in mice. Antimicrob. Agents Chemother., 2000, 44(10), 2919-2921.
207. Mah FS.Fourth-generation fluoroquinolones: new topical agents in the war on ocular bacterial infections. Curr. Opin. Ophthalmol., 2004, 15, 316-320.
208. Hwang DG.Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones. Surv. Ophthalmol., 2004, 49 (Suppl. 2), S79-S83.
209. Kowalski RP, et al.Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates. Am. J. Ophthalmol., 2003, 136, 500-505.
210. Callegan MC, et al.Antibacterial activity of the fourth-generation fluoroquinolones gatifloxacin and moxifloxacin against ocular pathogens. Adv. Ther., 2003, 20, 246-252.
211. Dajcs JJ, et al.Effectiveness of ciprofloxacin, levofloxacin, or moxifloxacin for treatment of experimental Staphylococcus aureus keratitis. Antimicrob. Agents Chemother., 2004, 48, 1948-1952.
212. Mather R, et al.Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am. J. Ophthalmol., 2002, 133, 463-466.
213. Müller HP, et al.In vitro antimicrobial susceptibility of oral strains of Actinobacillus actinomycetemcomitans to seven antibiotics. J. Clin. Periodontol., 2002, 29, 736-742.
214. Sobottka I, et al.In vitro activity of moxifloxacin against bacteria isolated from odontogenic abscesses. Antimicrob. Agents Chemother., 2002, 46, 4019-4021.
215. Eick S, Seltmann T, Pfister W.Efficacy of antibiotics to strains of periodontopathogenic bacteria within a single species biofilm-an in vitro study. J. Clin. Periodontol., 2004, 31, 376-383.
216. Eick S, et al.In vitro antibacterial activity of fluoroquinolones against Porphyromonas gingivalis strains. J. Antimicrob. Chemother., 2004, 54, 553-556.
217. Schulz H-H, Schlimbach G.Use of chemotherapeutic agents. 1999. WO/01/45679 A2.
218. Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin. Pharmacokinet., 2001, 40, 169-187.
219. Dalhoff A, Schmitz FJ. In vitro antibacterial activity and pharmacodynamics of new quinolones. Eur. J. Clin. Microbiol. Infect. Dis., 2003, 22, 203-221.
220. Wise R.A review of the clinical pharmacology of moxifloxacin, a new 8-methoxyquinolone, and its potential relation to therapeutic efficacy. Clin. Drug Invest., 1999, 17, 365-387.
221. MacGowan AP.Pharmacodynamics of Moxifloxacin. In: Moxifloxacin in Practice, Vol. 2. Adam D, Finch R (Eds.). Maxim Medical: Oxford, 1999, pp. 5-15.
222. Stass H, et al.Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects. Antimicrob. Agents Chemother., 1998, 42, 2060-2065.
223. Stass H, Kubitza D.Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J. Antimicrob. Chemother., 1999, 43 (Suppl. B), 83-90.
224. Andrews J, et al.Penetration of moxifloxacin into bronchial mucosa, epithelial lining fluid and alveolar macrophages following a single, 400-mg oral dose. In: 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. A 29. San Diego, 1998.
225. Stass H.Distribution and tissue penetration of moxifloxacin. Drugs, 1999, 58 (Suppl. 2), 229-230.
226. Stass H, et al.Pharmacokinetics of moxifloxacin, a novel 8-methoxy-quinolone, in patients with renal dysfunction. Br. J. Clin. Pharmacol., 2002, 53, 232-237.
227. Stass H, Kubitza D, Wensing G.Pooled analysis of pharmacokinetics, safety and tolerability of single oral 400 mg moxifloxacin (MFX) doses in patients with mild and moderate liver cirrhosis (LC). In: 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 2269. Toronto, 2000.
228. Sullivan JT, et al.The influence of age and gender on the pharmacokinetics of moxifloxacin. Clin. Pharmacokinet., 2001, 40 (Suppl. 1), 11-18.
229. Stahlmann R, Lode H.Fluoroquinolones in the elderly: safety considerations. Drugs Aging, 2003, 20, 289-302.
230. Scheld W.Maintaining fluoroquinolone class efficacy: review of influencing factors. Emerg. Infect. Dis., 2003, 9, 1-9.
231. MacGowan AP.In vitro models of infection: pharmacokinetic/pharmacodynamic correlates. In: First International Moxifloxacin Symposium. Mandell L (Ed.). Springer-Verlag: Berlin, 1999, pp. 104-110.
232. Wise R.Maximizing efficacy and reducing the emergence of resistance. J. Antimicrob. Chemother., 2003, 51 (Suppl. 1), 37-42.
233. Lode H, Garau J.Improving care for patients with respiratory tract infections. J. Chemother., 2002, 14 (Suppl. 2), 22-28.
234. Everett MJ, Piddock LJV.Mechanisms of resistance to fluoroquinolones. In: Quinolone Antibacterials. Kuhlmann J, Dalhoff A, Zeiler H-J (Eds.) Springer: Berlin, Heidelberg, New York, Barcelona, Budapest, Hong Kong, London, Milan, Paris, Santa Clara, Singapore, Tokyo, 1998, pp. 259-296.
235. Piddock LJ.Mechanisms of fluoroquinolone resistance: an update 1994-1998. Drugs, 1999, 58 (Suppl. 2), 11-18.
236. Wise R.A review of the mechanisms of action and resistance of antimicrobial agents. Can. Respir. J., 1999, 6 (Suppl. A), 20A-22A.
237. Barman Balfour JA, Lamb HM.Moxifloxacin: a review of its clinical potential in the management of communityacquired respiratory tract infections. Drugs, 2000, 59, 115-139.
238. Martinez-Martinez L, Pascual A, Jacoby GA.Quinolone resistance from a transferable plasmid. Lancet, 1998, 351 (9105), 797-799.
239. Wang M, et al.Plasmid-mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China. Antimicrob. Agents Chemother., 2003, 47, 2242-2248.
240. Wang M, et al.Emerging plasmid-mediated quinolone resistance associated with the qnr gene in Klebsiella pneumoniae clinical isolates in the United States. Antimicrob. Agents Chemother., 2004, 48, 1295-1299.
241. Dalhoff A.Dissociated resistance among fluoroquinolones. In: 2nd European Congress of Chemotherapy, Abstract T 160. Hamburg, 1998.
242. Dalhoff A.Lack of in vivo emergence of resistance against BAY 12-8039 in S. aureus and S. pneumoniae. In: 8th International Congress on Infectious Diseases, Poster No. 47.003. Boston, 1998.
243. Pong A, et al.Activity of moxifloxacin against pathogens with decreased susceptibility to ciprofloxacin. J. Antimicrob. Chemother., 1999, 44, 621-627.
244. Lu T, Zhao X, Drlica K.Gatifloxacin activity against quinolone-resistant gyrase: allele-specific enhancement of bacteriostatic and bactericidal activities by the C-8-methoxy group. Antimicrob. Agents Chemother., 1999, 43, 2969-2974.
245. Drlica K, Malik M.Fluoroquinolones: action and resistance. Curr. Top. Med. Chem., 2003, 3, 249-282.
246. Sindelar G, et al.Mutant prevention concentration as a measure of fluoroquinolone potency against mycobacteria. Antimicrob. Agents Chemother., 2000, 44, 3337-3343.
247. Dong Y, et al.Fluoroquinolone action against mycobacteria: effects of C-8 substituents on growth, survival, and resistance. Antimicrob. Agents Chemother., 1998, 42, 2978-2984.
248. Dong Y, et al.Effect of fluoroquinolone concentration on selection of resistant mutants of Mycobacterium bovis BCG and Staphylococcus aureus. Antimicrob. Agents Chemother., 1999, 43, 1756-1758.
249. Zhao X, Drlica K.Restricting the selection of antibiotic-resistant mutant bacteria: measurement and potential use of the mutant selection window. J. Infect. Dis., 2002, 185, 561-565.
250. Blondeau JM, et al.Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother., 2001, 45, 433-438.
251. Li X, Zhao X, Drlica K.Selection of Streptococcus pneumoniae mutants having reduced susceptibility to moxifloxacin and levofloxacin. Antimicrob. Agents Chemother., 2002, 46, 522-524.
252. Metzler K, et al.Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and-resistant Staphylococcus aureus. Int. J. Antimicrob. Agents, 2004, 24, 161-167.
253. Sprandel KA, Rodvold KA.Safety and tolerability of fluoroquinolones. Clin. Cornerstone, 2003, Suppl. 3, S29-S36.
254. Ball P.Future of the quinolones. Semin. Respir. Infect., 2001, 16, 215-224.
255. Talan DA.Clinical perspectives on new antimicrobials: focus on fluoroquinolones. Clin. Infect. Dis., 2001, 32 (Suppl. 1), S64-S71.
256. von Keutz E, Schlüter G.Preclinical safety evaluation of moxifloxacin, a novel fluoroquinolone. J. Antimicrob. Chemother., 1999, 43 (Suppl. B), 91-100.
257. Culley CM, et al.Moxifloxacin: clinical efficacy and safety. Am. J. Health Syst. Pharm., 2001, 58, 379-388.
258. Iannini PB, et al.Reassuring safety profile of moxifloxacin. Clin. Infect. Dis., 2001, 32, 1112-1114.
259. Lode H, Vogel F, Elies W.Grepafloxacin: a review of its safety profile based on clinical trials and postmarketing surveillance. Clin. Ther., 1999, 21, 61-74.
260. Lode H, Vogel F, Elies W.Clinical safety profile of grepafloxacin. Drugs, 1999, 58 (Suppl. 2), 395-396.
261. Ball P, et al.A new respiratory fluoroquinolone, oral gemifloxacin: a safety profile in context. Int. J. Antimicrob. Agents, 2004, 23, 421-429.
262. Strehl E, Hofmann C.Struktur-Wirkungs-Beziehungen und Nebenwirkungen von Chinolon-Derivaten. Krankenhauspharmazie, 2001, 22, 359-366.
263. Stahlmann R, Lode H. Toxicity of quinolones. Drugs, 1999, 58 (Suppl. 2), 37-42.
264. Vohr H-W, Wasinska-Kempka G, Ahr HJ.An investigation into the phototoxic potential of moxifloxacin. In: Moxifloxacin in Practice, Vol. 2. Adam D, Finch R (Eds.). Maxim Medical: Oxford, 1999, pp. 83-90.
265. Ball P.Quinolone-induced QT interval prolongation: a not-so-unexpected class effect. J. Antimicrob. Chemother., 2000, 45, 557-559.
266. Stahlmann R, Shakibaei M.Fluorchinolon-induzierte Tendopathien-klinische und experimentelle Aspekte. Chemother. J., 2000, 9, 140-147.
267. Stahlmann R.Clinical toxicological aspects of fluoroquinolones. Toxicol. Lett., 2002, 127, 269-277.
268. Stass H, Kubitza D.Lack of pharmacokinetic interaction between moxifloxacin, a novel 8-methoxyfluoroquinolone, and theophylline. Clin. Pharmacokinet., 2001, 40 (Suppl. 1), 63-70.
269. Stass H, et al.Lack of influence of itraconazole (ITR) on moxifloxacin (MFX) pharmacokinetics in healthy male subjects. In: 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 2270. Toronto, 2000.
270. Stass H, et al.Effect of calcium supplements on the oral bioavailability of moxifloxacin in healthy male volunteers. Clin. Pharmacokinet., 2001, 40 (Suppl. 1), 27-32.
271. von Keutz E, Schlüter G.Moxifloxacin and the liver: results of preclinical investigations. In: Moxifloxacin in Practice, Vol. 2. Adam D, Finch R (Eds.). Maxim Medical: Oxford, 1999, pp. 1-4.
272. Stass H, Kern A.Moxifloxacin-review of clinical pharmacokinetics: metabolism and excretion. In: 6th International Symposium on New Quinolones; Abstract No. 132. Denver, Colorado, 1998.
273. Kern A, et al.BAY 12-8039, a new 8-methoxyquinolone: metabolism in rat, monkey and man. In: 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract. No. F-023. New Orleans, USA, 1996.
274. Wetzstein H-G, et al.Degradation of ciprofloxacin by basidiomycetes and identification of metabolites generated by the brown rot fungus Gloeophyllum striatum. Appl. Environ. Microbiol., 1999, 65, 1556-1563.
275. Martens R, et al.Degradation of the fluoroquinolone enrofloxacin by woodrotting fungi. Appl. Environ. Microbiol., 1996, 62, 4206-4209.
276. Wetzstein H-G, Schmeer N, Karl W.Degradation of the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum: identification of metabolites. Appl. Environ. Microbiol., 1997, 63, 4272-4281.
277. Wetzstein H-G, et al.Residual antibacterial activity of metabolites derived from the veterinary fluoroquinolone enrofloxacin. In: 100th General Meeting of the American Society for Microbiology. Los Angeles, 2000.
278. Wetzstein H-G, Dalhoff A, Karl W.BAY 12-8039, A new 8-methoxyquinolone, is degraded by the brown rot fungus Gloephyllum striatum. In: 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract F 157. Toronto, 1997.
279. Gray JL, et al.Synthesis and testing of non-fluorinated quinolones (NFQs). A study on the influence of the C6 position. In: 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 1506. Toronto, 2000.
280. Barry AL, Fuchs PC, Brown SD.In vitro activities of three nonfluorinated quinolones against representative bacterial isolates. Antimicrob. Agents Chemother., 2001, 45, 1923-1927.
281. Ledoussal B, et al.Discovery, structure-activity relationships and unique properties of non-fluorinated quinolones (NFQs). Current Med Chem-Anti-Infective Agents, 2003, 2, 13-25.
282. Kim OK, Ohemeng K, Barrett JF.Advances in DNA gyrase inhibitors. Expert Opin. Investig. Drugs, 2001, 10, 199-212.
283. Kastner M, et al.Concentrations of the des-F(6)-quinolone garenoxacin in plasma and joint cartilage of immature rats. Arch. Toxicol., 2004, 78, 61-67.
284. Bartel S, et al.Possibly substituted 8-cyano-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids and their derivatives. 1996. Bayer AG: WO 97/31001.
285. Himmler T, et al.Synthesis and in vitro activity of pradofloxacin, a novel 8-cyanofluoroquinolone. In: 42nd ICAAC Abstracts, American Society for Microbiology, p. 188, Abstract: F-566. San Diego, CA, 2002.
286. Zerva L, Marshall SA, Jones RN.Premafloxacin: a projected veterinary use fluoro-quinolone with significant activity against multi-resistant gram-positive human pathogens. J. Antimicrob. Chemother., 1996, 38, 742-744.
287. Watts JL, et al.In vitro activity of premafloxacin, a new extended-spectrum fluoroquinolone, against pathogens of veterinary importance. Antimicrob. Agents Chemother., 1997, 41, 1190-1192.