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.

The high reactivity of ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates is governed by the simultaneous presence of the 4-OH and 2-C=O groups in the pyridine part of the molecule.Ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates are known to be quite powerful acylating agents. They readily react with primary and many secondary aliphatic, aromatic, and heterocyclic amines to form the corresponding amides in high yields [2][3][4][5]. The almost unlimited potential for modification of the quinolone and amide parts of the molecule allows a targeted change to the physicochemical and hence biological properties of the indicated compounds. This has led to increased interest from the viewpoint of chemists and pharmacologists engaged in a search for novel biologically active compounds based on them and which can give rise to medicinal compounds with improved properties There is also interest in the theoretical question regarding the reason for the high reactivity of the ethyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates which are key in such investigations because the reason remains unclear. Our report attempts to answer the question.The first step in our investigation was a comparative analysis of the steric structural features of the simplest member of the homologous series, i.e. ester 1 and of the isomers 4-ethoxycarbonyl-3-hydroxy-2-oxo-1,2-dihydroquinoline (2) and 3-ethoxycarbonyl-4-hydroxy-1-oxo-1,2-dihydroisoquinoline (3) stable to amidation. With this aim, all three esters were studied by X-ray structural analysis. Hence in the case of the isoquinoline derivative 3 it was found that the heterocyclic fragment is planar to within 0.022 Å (see Fig.

A preparative method has been developed for the synthesis of 1-hydroxy-3-oxo-5,6-dihydro-3H pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid hydrazide and its derivatives. The results of a study of the antitubercular activity of the synthesized compounds are presented.Hydrazine derivatives occupy a special place in the chemotherapy of tuberculosis which is one of the most dangerous contemporary infectious illnesses. Thus isonicotinic acid hydrazide has been used in medical practice for more than half a century under the name of isoniazid and it has not lost its value to the present day [2]. Further, on its basis it has given rise to phthivazid, saluzid, metazid [3] and there continue to be discovered modified analogs with improved pharmacological properties (e.g. flurenizid [4]). Rifampicin and rifapentin are amongst the most effective semi-synthetic antitubercular agents and they also contain a hydrazine fragment in their structure [2].In continuing our systematic search for potential agents amongst amidated 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids we repeatedly noted the high activity of the corresponding hydrazides [5], in particular the benzylidenehydrazides [6][7][8], in relation to the stimulation of tubercular and non-tubercular micobacteria. Following on in this area and with the aim of revealing a structure biological activity relationship in the studied series this report concerns tricyclic analogs of 4-hydroxy-2-quinolones and particularly the 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid derivative.Ethyl 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylate (1) reacts with hydrazine hydrate in alcohol solution at room temperature to give the hydrazine 2 in virtually quantitative yield. An attempt to purify this material by crystallization from DMF led to a very unexpected result. Immediately _______ * For Communication 125 see [1].

No abstract