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.
Various methods of synthesizing amides of 2-hydroxy-4-imino-1,4-dihydroquinoline-3-carboxylic acids have been studied. Results of investigations on the antitubercular and antiinflammatory activity of the obtained compounds are discussed.Amides are a class of organic compounds which are rightfully considered to be most convenient for carrying out investigations devoted to the search for rules on structure-pharmacological activity links. The basis for such a conclusion is the fact that the amide group is an important component of many biologically active substances, both natural and synthetic. The enormous variety of methods and procedures used in the synthesis of amides, and also the practically unlimited selection of starting materials, enables systematic changes to be introduced into the structure of the final compounds, thereby purposefully changing their physicochemical and biological properties.Proceeding from this, one of the stages of our investigations was devoted to the amide of 4-amino-2-oxoquinoline-3-carboxylic acids. As one of the proposed variants of obtaining such compounds we studied the possibility of synthesizing amides of 1H-4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylic acid 1, which then might be transformed into the 4-amino derivative by any suitable method.Previous attempts to obtain amides 1 by the reaction of 4-chloro acid 2a with amines in the presence of N,N'-dicyclohexylcarbodiimide were unsuccessful [2]. Activation of the acid component of acid 2a with N,N'-carbonyldiimidazole (CDI) also gave no positive result. It turned out that on interacting 4-chloro-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (2a) with N,N'-carbonyldiimidazole in anhydrous DMF the vigorous evolution of CO 2 characteristic of this reaction was observed, obviously indicating the formation of acylimidazole 3 (Scheme 1).
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: amides, 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylic acids, tricarbonylmethane heterocyclic derivatives, diuretic activity, X-ray structural analysis.The problem of discovering novel classes of chemical substances capable of diuretic action, and particularly important, those which are highly efficient and safe diuretic medicines has not lost its urgency even over recent decades. Interesting substances investigated within this scheme are amidated 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids derivatives [2,3]. Although for a long time high diuretic activity has not been considered a characteristic of quinolone compounds, several of these materials proved extremely promising and have been subjected to broad pharmacological investigation to this time. With this in mind we have carried out the synthesis and biological screening to reveal the ability of the series of structurally related 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid N-R-amides 1-3 to increase the diuretic kidney function.It was found that the alkylamides 1a-u (Table 1) can be prepared by the reaction of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate (4) with a two, or better three, fold excess of the corresponding alkylamine in refluxing ethanol. It was initially proposed that it was necessary to use quite a large excess of the _______ * For Communication 143 see [1].
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.