Quinolones fused

A single quinolone-fused oxepine 45 was reported in a study on the gold (I)-catalyzed formation of functionalized quinolones (130L4234).The starting 2-alkynylarylazide derivatives such as 44 undergo a 1,3-acetoxy shift, followed by cyclization of the azide and a ring-expansion via a 1,2-shift. 

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. 

A -cyclopropylquinolone 63 and iV-fused pyrrolidinyl 66 and piperidinyl 69 quinolones were reported as intermediates for the preparation of potent antibacterial agents. Use of acids as reaction solvent allow for the cyclization of these iV-substituted... 

Pemberton N, Chorell E, Almqvist F (2006) Microwave-Assisted Synthesis and Functionalization of 2-Pyridones, 2-Quinolones and Other Ring-Fused 2-Pyridones. T. 1-30... 

Keywords 2-Pyridone 2-quinolone Ring-fused 2-pyridone... 

Fig. 1 Heterocycles bearing a 2-pyridone moiety with wide range of medicinal applications. Amrinone WIN 40680 1 is a cardiotonic agent for the treatment of heart failure. ZAR-NESTRA 2 is a selective farnesyl protein inhibitor and NP048 3 is a pilicide with novel antibacterial properties. The 2-pyridones 4, 5 and 6 are schematic representations of the three categories of 2-pyridones that wiU be covered in this chapter i.e., substituted 2-pyridones 4, 2-quinolones 5 and other ring-fused 2-pyridones 6...

Table 2 A comparison between conventional heating and microwave-assisted synthesis in an intramolecular Heck coupling to heterocyclic derivatives of 2-quinolones 20 and 21. Note the high selectivity in (b), where two possibilities exist to fuse a six-membered ring...

Regioselective hydrolysis of the diester 27 gave the 1,3-thiazetidine 28 where the thiazetidine ring is fused to a quinolone nucleus <99CPB1765>. Derivatives of the tricyclic system, e.g. 29, showed activity against gram-positive bacteria including quinolone-resistant MRS A <99H(51)2915>. 

A prototypical series of monocyclic and tricyclic agents with potency in the nalidixic acid - oxolinic acid range has been reported [89]. The enantiomers of the tricycle (55), which lacks the ring fused to the 5- and 6-positions of the pyridine portion common to most quinolones, have been evaluated in vitro, and... 

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

The use of classical condensation reactions is important. Thus, the Dieckmann reaction (equation 38) and the Thorpe-Ziegler cyclization (equation 39) have been used for almost a century for the preparation of a wide range of monocyclic and benzo-fused heterocycles. The aldol condensation and related reactions have also been fairly widely exploited, especially for the synthesis of 4-quinolones (the Camps reaction, e.g. equation 40), and various extensions of this general approach are described in the monograph chapters. 

Very much the same strategy is used to synthesize a quinolone that contains an additional fused ring. This agent features a broad-spectrum antibacterial activity in spite of the lack of a nitrogen substituent at position 7. It is of note in this case... 

A large number of tricyclic fluoroquinolones, in which the 1,3-thiazetidine moiety is fused to the quinolone, have been reported as good antibacterial agents, for example, prulifloxacin, displaying a broad spectrum with low toxicity. 

Six quinolone antibiotics (including ciprofloxacin) were separated and determined by CE on fused-silica capillaries (57 cm x 75 pm i.d. 50 cm to detector) at 25°C, with injection on the anode side, an applied voltage of 10 kV, and detection at 280 nm [56], The buffer was 100 mM HEPES/ acetonitrile (9 1). The calibration graphs were linear from 0.25 to 40 pg/mL and detection limits were approximately 0.25 ng/mL. 

Fourteen quinolone antibacterial compounds (including ciprofloxacin) were separated by fused-silica column (59 cm x 50 pm i.d. 43 cm to detector) at 30 kV in less than 8 min and monitored at 260 nm [60], In this method, a background electrolyte of pH 7.3 containing 32 mM borate, 39 mM cholate, 8 mM heptanesulfonate, and 18 mM phosphate (as the sodium salts), modified with 28% acetonitrile, was used as running buffer. 

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