The Chemistry of the Quinolones: Methods of Synthesizing the Quinolone Ring System

Synthesis and antibacterial properties of new N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids

“…The required synthon (4), substituted 4(1H)-oxoquinoline-3-carboxylic acid, is prepared from 2,4-dichloro-5-fluoro-3-nitrobenzoic acid and ethyl 3-(dimethylamino)-acrylate according to a reported procedure. 30,31 Over the last two decades, a plethora of secondary amines [1][2][3][4][5] and amino alcohols 32 were introduced at C-7 of 6-fluoro-4-oxoquinoline-3-carboxylic acid for enhancement of the antibacterial activity, attainment of good safety profile and optimal blend of favourable bioproperties. However, incorporation of α-amino acids thereat is limited to two reports on the glycine derivatives (10 and 11; Scheme 2).…”

“…ciprofloxacin 1a) represent a successful achievement towards the design and development of potent anti-infectious drugs. [1][2][3][4][5] Some derivatives such as 7-(4-arylpiperazin-1-yl)-6-fluoro-8-trifluoromethylquinolones, for example 1b, were reported to act as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1 reverse transcriptase. [6][7][8][9] 1a (R 1 = c-C 3 H 5 ; R 2 On the other hand, simple or heterocyclic-fused quinoxalinones have become interesting compounds for study as antiviral agents [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] exemplified by the 3,4-dihydroquinoxalin-2-one core (2, Y=O), a second generation of NNRTIs, that is opaviraline (2a) [22][23][24][25][26][27] and the related 2-thione talveraline (2b), [14][15][16][17][18][19] are in clinical development.…”

Three quinolone compounds featuring O...I halogen bonding

“…Quinolones have been thoroughly investigated since the early 1960s as potent antibacterial agents (Andriole, 1998). Many quinolone structures have been characterized and quinolone chemistry has been well explored (Grohe, 1998). A search of the Cambridge Structural Database (CSD;Version 5.30, with May 2009 updates;Allen, 2002) revealed 267 solidstate structures containing the quinolone moiety, 201 of which are halogenated, of which 61 contain Cl, 5 contain Br and only one contains I (CSD refcode BARTIX; Keller et al, 1981).…”

Von der Nalidixinsäure zu den Chinolonen der dritten Generation: Die Evolution der Chinolone

“…Für die Synthese des Chinolon-Grundgerüstes [1] spielen im wesentlichen 2 Methoden eine Rolle: Die klassische GouldJacobs-Reaktion, nach der ausgehend von substituierten Anilinen u.a. Norfloxacin (6) oder Ofloxacin (5) …”

“…Ein besonderer Impuls für die Chinolon-Forschung kam von der neuen Synthese, der Grohe-Methode [1], durch die der Cyclopropylring in Ciprofloxacin (8) eingeführt werden konnte und die Anstoß für die Herstellung einer Vielzahl neuartiger Forschungs-und Entwicklungsprodukte war. Die Bemühungen zur Strukturvariation bezogen sich in den letzten 15 Jahren aber nicht nur auf Abwandlungen des Grundkörpers, sondern in verstärktem Maße auch auf die Suche nach neuartigen cyclischen Aminen als Substituenten für die 7-Position [2].…”