4-quinolone-3-carboxylic

Recent research on 4-quinolone-3-carboxylates has led to discovery of the fluoroquinolones, which are second-generation quinolones and include ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, norfloxacin, ofloxacin, and sarafloxacin. The main difference between classic quinolones and the fluoroquinolones is that the latter contain a fluorine atom at the C-3 position and a piperazinyl group at the C-7 position (Fig. 3.6). 

Fasani E, Barberis Negra FF, Mella M, Monti S, Albini A. Photoinduced C-F bond cleavage in some fluorinated 7-amino-4-quinolone-3-carboxylic acids. J Org Chem 1999 64 5388-5395. 

The alternative Scheme B is based on A-nucleophilic attack. Thus, bubbling air through a boiling solution of ethyl 3-amino-2-(quinoxaline-2-carbonyl)crotonoate 66 in DMF furnishes pyrido[2,3-Zr]quinoxaline 67 (Scheme 20) (04RCB1267). The latter has a structural similarity to derivatives of 4-quinolone-3-carboxylic acid, well known because of their high antibacterial activity. 

Features of antibacterial action of derivatives of 4-quinolone-3-carboxylic acid 93KFZ(5)4. 

Leysen DC, et al. Synthesis of antibacterial 4-quinolone-3-carboxylic acids and their derivatives. Part 1. Pharmazie,... 

Oxolinic Acid, 5-Efhyl-5,8-di/iyd -8-oxo-i,J-dioxolo[4,5-g]quirtoline-7-carboxcylic acid I-ethyl-1,4-dihydro -6,7 -methylenedioxy -4 -oxo -3 -quinolinecarboxylic add 1 -ethyl -6,7 -methylenedioxy -4-quinolone -3 -carboxylic add W 4565 Emyrenil Nidantin Ossian Oxoboi Pietil Pro-doxol Urinox Uritratc Uro-Alvari Urotrute Uroxin Von Boch Uroxol Utibid. CuH.-NO, mol wt 261.24. C 59.77%, H 4.25%, N 5.36%, O 30.62%. Quioolone antibacterial. Prepn Kaminsky, Meltzer, U.S. pat. 3,287,458... 

Many quinoline derivatives are important biologically active agents. 8-Hydroxyquinoline and some of its halogenated derivatives are used as antiseptics. Chloroquine 111 is one of the older but still important antimalarials. A -Alkyl-4-quinolone-3-carboxylic acid and systems derived therefrom are constituents of antibacterials (gyrase inhibitors [112]) such as nalidixic acid 112, ciprofloxazin 113 and moxifloxazin 114. The quinoline-8-carboxylic acid derivative 115 (quinmerac) is employed as a herbicide for Galium aparine and other broad-leaved weeds. Methoxatin 116, known as coenzyme PQQ is a heterotricyclic mammalian cofactor for lysyl oxidase and dopamine P-hydroxylase [113]. 

Equal amounts of diethyl ethylphenylaminomethylenemalonate and PgOg suspended in nitrobenzene, heated to ca. 120-140°, whereupon an exothermic reaction raises the temp, to 160-190°, cooled slightly, and a small amount of water added N-ethyl-4-quinolone-3-carboxylic acid. Y 96%. F. e. s. D. G. Markees and L. S. Schwab, Helv. 55, 1319 (1972). 

Yoshikazu A, Kazuhiko I, Fujio I, Masaki H, Takayoshi 1 (2005) Synthesis and antibacterial activity of l-(2-fluorovinyl)-7-substituted-4-quinolone-3-carboxylic acid derivatives, confor-mationaUy restricted analogues of fleroxacin. J Med Chem 48 3194-3202... 

Cociorva O, Li B, Nomanbhoy T, Li Q, Nakamura A, Nakamura K, Nomura M, Okada K, Seto S, Yumoto K, Liyanage M, Zhang M, Aban A, Leen B, Szardenings A, Rosenblum J, Kozarich J, Kohno Y, Shreder K (2011) Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-36. Bioorg Med Chem Lett 21 5948-5951... 

Quinolone carboxylic acids are a class of totally synthetic antibacterial agents which have the general structure (1). 

In the final stage, as depicted in Scheme 10, the BOC-protected compound 45 and the quinolone carboxylic acid 27 are heated in DMSO under tri-ethylamine, followed by deprotection of the terf-butoxycarbonyl group under acidic condition to afford the final product DQ-113 (26). 

Quinolone carboxylic acid antibacterials are synthetic compounds whose basic nuclear structure includes a quinolone ring and a carboxylic acid group. Fluoroquinolones are second-generation quinolones that contain in their molecule a fluorine and a piperazine ring. Quinolones are amphoteric compounds slightly soluble in polar solvents such as water, and insoluble in nonpolar solvents such as benzene and hexane. Most of these drugs are fluorescent and are quite stable in aqueous solution toward light, except miloxacin, which is reported to be unstable. 

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,... 

Petersen U, et al. The synthesis and biological properties of 6-fluoro-quinolone-carboxylic acids. Bull. Chim. Soc. Belg, 1996, 105, 683-699. 

Kim WJ, et al. Novel quinolone carboxylic acid derivatives and process for preparing the same. 1994. Korea Res. Inst. Chem. Technology EP 622 367. 

Pyridyl quinolone carboxylic acids, (V), and 7-piperazine quinazolin-2,4-dione derivatives, (VI), prepared by Park (5) and Domagala (6), respectively, exhibited broad-spectrum antibacterial activity with reduced cytotoxicity. 

Quinolone and fluoroquinolone antibiotics are a group of highly-potent, synthetic antibiotics, derived from 3-quinolone carboxylic acid They are used as broad-spectrum antibiotics in the treatment of both human and veterinary diseases. 

Cholinergic receptor agonists Muscarinic receptors Benzyl quinolone carboxylic acid analogs Cevimeline EUK1001 Lanomeline Vedaclidine Nicotinic receptors Nicotinic analog ZY-1... 

Mistry SN, Valant C, Sexton PM, Capuano B, Christopoulos A, Scammells PJ (2013) Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the Ml muscarinic receptor. J Med Chem 56 5151-5172... 

A related strategy was suggested in which one of the reactants is attached via a linker to tetrabenzo[a,c,g,i]fluorene (Tbf). The reaction product can now be purified by taking advantage of the high affinity of Tbf to charcoal in polar solvents (mixture of DCM and methanol). Desorption can be affected with non polar solvents such as toluene [144]. The method was exemplified by the synthesis of a quinolone carboxylic acid derivative (ciprofloxacin). 

Notarianni, L.J. Jones, R.W. Method for the determination of ofloxacin, a quinolone carboxylic acid antimicrobial, by high-performance liquid chromatography. J.Chromatogr., 1988, 431, 461-464... 

Modifications of the Gould-Jacobs reaction have led to many versatile quinolone syntheses. In Table V, entry 4, ring closure of the tertiary en-aminone fails in a high-boiling solvent, but gives the quinolone carboxylic acid with a catalytic amount of phosphorus pentoxide or polyphosphoric acid in refluxing nitrobenzene. This modification is now generally applied to the preparation of quinolones from tertiary enaminones such as the fused quinolone, entry 5 (an important intermediate for fluoroquinolone antibacterials). 

Quinolone - quinolone carboxylic acid (C12H11NO3) Quinolone - temafloxacin (C21H18F3N3O3)... 

For examples of quinolone antibiotics we can choose ofloxacin, whose synthesis was discussed in detail in Chapter 22, and rosoxacin, whose synthesis is discussed below. Both molecules contain the same quinolone carboxylic acid framework, outlined in black, with another heterocyclic system at position 7 and various other substituents here and there. 

We have examined the application of this media for improving purification efficiency of quinolone carboxylic acids and short peptides which were prepared in rapid microwave assisted synthesis. 

Naoki O, Toshifumi A (2003) Process for producing antibacteriril quinolone-carboxylic acid... 

Ganapati Reddy P, Baskaran S (2001) Microwave assisted amination of quinolone carboxylic acids an expeditious synthesis of fluoroquinolone antibacterials. Tetrahedron Lett 42 6775-6777... 

Yang F, Shipe W, Bunda J, Nolt M, Wisnoski D, Zhao Z, Barrow J, Ray W, Ma L, Wittmann M, Seager M, Koeplinger K, Hartman G, Lindsley C (2010) Parallel synthesis of M-biaryl quinolone carboxylic acids as selective Mi positive allosteric modulators. Biooig Med Chem... 

Trkovnik M, Ivezic Z (2000) Synthesis of some new coumarin-quinolone carboxylic acids. J Heterocycl Chem 37 137-141... 

For the synthesis of new-generation antibacterial quinolone carboxylic acids, reduction of a2aspiroketones by Phaeocrepsis sp. JCM 1880 afforded the corresponding (R)-alcohols in high ee as shown in Figure 11.10c [60,61]. 

Synthesis of an Intermediate for a New-Generation Antibacterial Quinolone For the synthesis of new-generation antibacterial quinolone carboxylic acids. 

A surprising development involving the 3-position has been presented (61,62). This position traditionally has had a carboxylic acid group and attempts to replace the carboxylate have resulted in lower antibacterial activity. However, it was demonstrated that the carboxylate could be replaced with an isothiazolo ring fused between the 2- and 3-position of the quinolone nucleus. A-62824 [111279-87-9] (22), illustrates this stmctural modification as apphed to ciprofloxacin. 

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