ERRATUMTo the article "4-Hydroxy-2-quinolones. 179. Synthesis, Structure, and Anti-inflammatory Activity of 4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-ylacetic Acid and its Derivatives" -I.

Keywords: alkylamides, 4-hydroxy-2-oxoquinoline-3-carboxylic acids, diuretic activity, anti-inflammatory activity, X-ray structural analysis.For transformation of ethyl 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylates (1) to alkyl-, aryl-, or hetarylamides (of interest as potentially biologically active materials) it was proposed to treat them with a 40% excess of the corresponding amine in refluxing bromobenzene over 20 h with subsequent distillation of solvent at reduced pressure and purification of the final reaction products [2]. At the same time, the high reactivity of 1-R-3-ethoxycarbonyl-4-hydroxy-2-oxo-1,2-dihydroquinolines has been noted and this allows them to be amidated quite efficiently [3][4][5]. The obvious structural similarity of ester 1 with these compounds led us to suggest that they will react with amines (at least aliphatic) under milder conditions.i R = C 5 H 11 , j R = i-C 5 H 11 , k R = 2-hydroxyethyl, l R = 3-hydroxypropyl, m R = cyclo-C 3 H 5 ,

Until recently 4-hydroxyquinolin-2-ones have not even mentioned as analgesics in scientific literature. Only some years ago the situation turned over when based on preliminary virtual screening we obtained hydrochlorides of [(alkylamino)alkyl]amides of 1-allyl-4-hydroxy-6,7dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid as potential opioid receptor antagonists [24]. Further pharmacological research has confirmed the presence of "calculated" Pain and Treatment 22 Pain and Treatment 24 Pain and Treatment 28

Keywords: 4-R-2-oxo-1,2-dihydroquinoline-3-carboxylic acids, pKa, analgesic activity, hydrolysis.Even a brief glance at the scientific literature and patent documentation for 4-hydroxy-2-quinolones shows a very broad range of biological properties typifying them. In the series of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids the overwhelming number of publications relate to N-R-amides and the products of their subsequent chemical transformations. Esters have been studied much less frequently and the acids themselves hardly at all. Such a situation becomes fully understandable if one actually takes into account the diverse and well tested arsenal of highly efficient methods for synthesizing the amide derivatives [2][3][4][5][6][7][8]. Not least is the unlimited choice and availability of intermediate derivatives available from chemical industry in such syntheses in the form of primary or secondary alkyl-, aryl-, and hetarylamines. Thanks to this there is a real opportunity for a targeted change of properties of the N-R-amides obtained within very broad limits and so for achieving optimum properties. This is of particular value when carrying out work to create novel biologically active materials. Quite a number of fundamentally different methods of preparing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids esters are well known [2][3][4][5][6][9][10][11][12]. However, all of these are only effective in relation to the lowest alkyl esters. In the reminder of the examples it is necessary to turn to special methods (e.g., high temperature transesterification [9]) but these are unfortunately characterized by low yields.

acid anilides has been carried out. The antitubercular activity and the effect on the urinary function of the kidney have been studied for the compounds prepared. A structure-biological activity relationship is discussed.In recent times the attention of synthetic chemists has been drawn to a search for biologically active substances in order to create from them novel medicinal compounds and it has been ever more attracted to 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides [2][3][4][5][6][7][8]. This is explained not only by the broad spectrum of pharmaceutical activity of the studied 4-hydroxyquinol-2-ones and their natural occurrence but also by the ready chemical modification of their basic structure. Directed changes can be introduced into any part of the basic molecule by quite simple methods guaranteeing the best access to an almost unlimited range of analogs which, in turn, significantly increases the likelihood of discovering promising structural leads in subsequent study.Condensation of primary aromatic amines with triethyl methanetricarboxylate in conventional conditions gives primarily the methanetricarboxylic acid trianilides. During microwave irradiation the reaction given occurs somewhat differently and indeed yields 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides [7]. To some extent, the low yields are compensated by the synthesis of the target compounds in a single stage. This method is certainly of interest although the promising application of it is small since both the quinolone ring and the anilide fragment are formed from the same aniline.