4-Hydroxy-2-quinolones. 177*. Study of a structure-diuretic activity relationship in a series of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid N-R-amides

Abstract

With the aim of deducing a structure-biological dependence we have carried out the synthesis of quinoline-3-carboxylic acid N-R-amides with a p-methoxyphenyl substituent in the amide part of the molecule. The effects of the compounds prepared on the excretory function of the kidney are discussed. Using a system of simplex descriptors and the method of tree type classification a QSAR model has been constructed which is suitable for prediction of the diuretic activity of novel quinolinecarboxylic acid N-R-amides.The ability of 4-hydroxy-2-quinolones to show clear diuretic activity was first discovered accidentally amongst 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid arylalkylamides about 20 years ago [2]. In later extended screening studies a similar type of biological activity was revealed in the closely structurally related amide derivatives of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-and also 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acids ([3-5] and [6-7] respectively). In this way it was possible to show several important structure-biological activity relationships. Firstly, the need was revealed for the presence of an aryl fragment in the amide part of the molecule. Secondly, it was experimentally confirmed that there was a marked increase in diuretic action with approach of the aryl ring to the amide nitrogen atom. Hence in the series 3-arylpropylamide → 2-arylethylamide → benzylamide → anilide with the same substituents in the aromatic ring the most active generally proved to be the anilide. Thirdly, the most powerful positive effect on

Methyl-substituted anilides of 4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carb-oxylic acid. Synthesis, spectral characteristics and biological properties

“…Из всех теоретически возможных изо-меров здесь внимание на себя обращает только 2,4-диметиланилид 2f, занимающий по уровню анальгетической активности промежуточную по-зицию между 2-и 4-монометильными производ-ными 2а и 2с соответственно. Структурное сходство анилидов 2а-h с обла-дающими высокой диуретической активностью 1-R-4-гидрокси-2-оксо-1,2-дигидрохинолин-3-карбоксанилидами [5][6][7][8][9][10][11] послужило теоретиче-ской предпосылкой для изучения их влияния и на мочевыделительную функцию почек. В дан-ном исследовании использована традиционная методика [12].…”

The Study of the Structure—Diuretic Activity Relationship in a Series of New N-(Arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo-[3,2,1-ij]quinoline-5-carboxamides

“…Therefore, it is not surprising that the ability to greatly increase urination accidentally discovered by our laboratory in some 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides I (Figure 2) [11], which was previously considered untypical for this class of chemical compounds, gave impetus to the purposeful search for new diuretics. In the studies, along with other various 4-hydroxyquinoline-2-one amides I [12][13][14][15] isosteric 4-chloro-(II), 4-methyl-(III) and 4-amino-(IV) derivatives [15][16][17][18], their analogs V hydrogenated in the benzene moiety of the molecule [19], as well as structurally similar 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides (VI) [20], and 4-hydroxy-2,2-dioxo-1H-2λ 6 ,1-benzothiazine-3-carboxanilides (VII) [21] were involved. [11][12][13][14][15] and bicyclic "me-too" clones II-VII [15][16][17][18][19][20][21].…”

“…In the studies, along with other various 4-hydroxyquinoline-2-one amides I [12][13][14][15] isosteric 4-chloro-(II), 4-methyl-(III) and 4-amino-(IV) derivatives [15][16][17][18], their analogs V hydrogenated in the benzene moiety of the molecule [19], as well as structurally similar 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamides (VI) [20], and 4-hydroxy-2,2-dioxo-1H-2λ 6 ,1-benzothiazine-3-carboxanilides (VII) [21] were involved. [11][12][13][14][15] and bicyclic "me-too" clones II-VII [15][16][17][18][19][20][21].…”

“…In general, highly active compounds were found in all groups I-VII without exception regardless of the structure of the underlying bicyclic heterocyclic system. However, much better results were [11][12][13][14][15] and bicyclic "me-too" clones II-VII [15][16][17][18][19][20][21].…”

Синтез, Гидролиз И Анальгетическая Активность 3-[3-(1-Арилэтилкарбамоил)-4-Гидрокси-2-Оксо-1,2-Дигидрохинолин-1-Ил]пропаннитрилов И Их Производных

“…Áèöèêëè÷åñêèé ôðàãìåíò, 4-ãèäðîêñèëüíàÿ, 2-êàðáîíèëüíàÿ è 3-êàðáîêñèëüíàÿ ãðóïïû äèêèñëîòû VII ëåaeàò â îäíîé ïëîñêîñòè ñ òî÷íîñòüþ 0,02 Å, ÷åìó ñïîñîáñòâóåò îáðàçîâàíèå ñèëüíûõ âíóòðèìîëåêóëÿðíûõ âîäîðîäíûõ ñâÿçåé Î(2)-Í···Î (3) [13].…”