Kirk-Othmer Encyclopedia of Chemical Technology 2000
DOI: 10.1002/0471238961.1721091418052113.a01
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Antibacterial Agents, Quinolones

Abstract: Quinolone carboxylic acids are a class of totally synthetic antibacterial agents which encompass 4‐oxo‐3‐quinolinecarboxylic acids as well as the corresponding 1,8‐naphthyridines, cinnolines, and pyrido [2,3‐ d ]‐pyrimidines. These classes are illustrated by ciprofloxacin, nalidixic acid, cinoxacin, and piromidic acid, respectively. Established quinolone antibacterial agents are ciprofloxacin, ofloxacin, enoxacin, norfloxacin, and pefloxacin. Quinolones exert their antibacterial activit… Show more

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Cited by 2 publications
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“…The principle issues with the existing drugs and drug classes were as follows: 1) the anthracycline class--of which doxorubicin was a member--caused significant cardiotoxicity by an unknown mechanism; 2) the epipodophyllotoxins--etoposide and tenoposide--were poorly soluble and therefore difficult to formulate; in particular an oral formulation of etoposide showed an unacceptably wide range of bioavailability; 3) the anthracyclines and epipodophyllotoxins showed a significant incidence of secondary (drug-induced) leukemias due to an unknown mechanism; 4) resistance, primarily due to P-glycoprotein (P-gp) mediated efflux, developed frequently, with cross-resistance observed to all of the topo II classes; 5) anthracycline and epipodophyllotoxin synthetic chemistry was laborious so that the capacity to generate new analogs to solve specific issues was sharply limited [ 119 - 126 ]. By contrast, the differentiated, and highly pre-optimized, quinolone scaffold held promise to solve at least some of these issues: 1) the quinolone class was typically regarded as quite safe overall, without any significant cardiotoxicity (although occasional tendonitis was seen as a class effect), 2) quinolones have good physicochemical properties, are straightforward to formulate for both oral and parenteral use and display excellent and predictable bioavailability and pharmacokinetics, 3) quinolones easily cross cell membranes (both eukaryotic and prokaryotic) with good accumulation and therefore efflux-based resistance might not emerge as a major issue; and finally 5) because quinolone chemistry is extremely straightforward, new analogs can be synthesized quickly during problem-solving and optimization phases, offering some confidence that a preclinical program might proceed rapidly [ 73 , 75 , 127 - 132 ].…”
Section: -1990: Two Separate Therapy Worlds Finally Collidementioning
confidence: 99%
“…The principle issues with the existing drugs and drug classes were as follows: 1) the anthracycline class--of which doxorubicin was a member--caused significant cardiotoxicity by an unknown mechanism; 2) the epipodophyllotoxins--etoposide and tenoposide--were poorly soluble and therefore difficult to formulate; in particular an oral formulation of etoposide showed an unacceptably wide range of bioavailability; 3) the anthracyclines and epipodophyllotoxins showed a significant incidence of secondary (drug-induced) leukemias due to an unknown mechanism; 4) resistance, primarily due to P-glycoprotein (P-gp) mediated efflux, developed frequently, with cross-resistance observed to all of the topo II classes; 5) anthracycline and epipodophyllotoxin synthetic chemistry was laborious so that the capacity to generate new analogs to solve specific issues was sharply limited [ 119 - 126 ]. By contrast, the differentiated, and highly pre-optimized, quinolone scaffold held promise to solve at least some of these issues: 1) the quinolone class was typically regarded as quite safe overall, without any significant cardiotoxicity (although occasional tendonitis was seen as a class effect), 2) quinolones have good physicochemical properties, are straightforward to formulate for both oral and parenteral use and display excellent and predictable bioavailability and pharmacokinetics, 3) quinolones easily cross cell membranes (both eukaryotic and prokaryotic) with good accumulation and therefore efflux-based resistance might not emerge as a major issue; and finally 5) because quinolone chemistry is extremely straightforward, new analogs can be synthesized quickly during problem-solving and optimization phases, offering some confidence that a preclinical program might proceed rapidly [ 73 , 75 , 127 - 132 ].…”
Section: -1990: Two Separate Therapy Worlds Finally Collidementioning
confidence: 99%
“…For the purpose of wider context, the following is a brief account of the key achievements over 5 decades in the antibacterial quinolone field after the launch of nalidixic acid. For further information on this subject the reader is directed to key reviews and books selected from a vast literature. Both quinolone and 1,8-naphthyridone based antibacterial drugs today are often informally included within the broad, generally interchangeable designations “quinolone” or “fluoroquinolone” antibacterial class; occasionally, the 1,8-naphthyridone core is referred to as an 8-azaquinolone. In the 15 or so years following the 1964 clinical introduction in the United States of nalidixic acid by Sterling Drug, a number of follow-on agents were launched by other companies (Sterling itself later launched two additional drugs from this class for human use, rosoxacin and amifloxacin).…”
Section: Introductionmentioning
confidence: 99%