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Derivatives of 3-(1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione unsubstituted on quinolone nitrogen atom, which are available by the previously described four step synthesis starting from aniline, were exploited as intermediates in obtaining the title compounds. The procedure involves the introduction of propargyl group onto the quinolone nitrogen atom of mentioned intermediates by the reaction of them with propargyl bromide in N,N-dimethylformamide (DMF) in presence of a potassium carbonate and the subsequent formation of a second triazole ring by copper catalyzed cyclisation reaction with azido compounds. The products were characterized by 1H, 13C and 15N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments (1H&ndash, 1H gs-COSY, 1H&ndash, 13C gs-HSQC, 1H&ndash, 13C gs-HMBC) with 1H&ndash, 15N gs-HMBC as a practical tool to determine 15N NMR chemical shifts at the natural abundance level of 15N isotope.

(1-(2,4-Dioxo-1,2,3,4-tetrahydroquinolin-3-yl)-1 H -1,2,3-triazol-4-yl)methyl acetates substituted on nitrogen atom of quinolinedione moiety with propargyl group or (1-substituted 1 H -1,2,3-triazol-4-yl)methyl group, which are available from the appropriate 3-(4-hydroxymethyl-1 H -1,2,3-triazol-1-yl)quinoline-2,4(1 H ,3 H )-diones unsubstituted on quinolone nitrogen atom by the previously described procedures, were deacetylated by acidic ethanolysis. Thus obtained primary alcohols, as well as those aforenamed unsubstituted on quinolone nitrogen atom, were oxidized to aldehydes on the one hand with pyridinium chlorochromate (PCC), on the other hand with manganese dioxide, and to carboxylic acids using Jones reagent in acetone. The structures of all prepared compounds were confirmed by 1 H, 13 C and 15 N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments ( 1 H– 1 H gs-COSY, 1 H– 13 C gs-HSQC, 1 H– 13 C gs-HMBC) with 1 H– 15 N gs-HMBC as a practical tool to determine 15 N NMR chemical shifts at the natural abundance level of 15 N isotope.

In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 mu M and against Mycobacterium bovis AN5A below 15 mu M but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox (TM) assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 mu M and a CC50 against MRC-5 of 67.4 mu M. (C) 2017 Elsevier Masson SAS. All rights reserved.

N-(α-Ketoacyl)anthranilic acids were prepared by oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones by using paraperiodic acid (H5IO6) or sodium periodate (NaIO4). The optimisation of the reaction conditions is described as well as the utilisation of N-(α-ketoacyl)anthranilic acids in the preparation of anthranilic acid hydrochlorides.

A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1 H )-ones into 4-(tetra- O -acetyl-β- d -glucopyranosyloxy)quinolin-2(1 H )-ones is reported. Four glycosyl donors including tetra- O -acetyl-α- d -glucopyranosyl bromide, β- d -glucose pentaacetate, glucose tetraacetate and tetra- O -acetyl-α- d -glucopyranosyl trichloroacetimidate were tested, along with different promoters and reaction conditions. The best results were obtained with tetra- O -acetyl-α- d -glucopyranosyl bromide with Cs 2 CO 3 in CH 3 CN. In some cases the 4-O-glucosylation of the quinolinone ring was accompanied by 2-O-glucosylation yielding the corresponding 2,4-bis(tetra- O -acetyl-β- d -glucopyranosyloxy)quinoline. Next, 4-(tetra- O -acetyl-β- d -glucopyranosyloxy)quinolin-2(1 H )-ones were deacetylated into 4-(β- d -glucopyranosyloxy)quinolin-2(1 H )-ones with Et 3 N in MeOH. In some instances the deacetylation was accompanied by the sugar–aglycone bond cleavage. Structure elucidation, complete assignment of proton and carbon resonances as well as assignment of anomeric configuration for all the products under investigation were performed by 1D and 2D NMR spectroscopy.

N-(α-ketoacyl)anthranilic acids reacted with phenylhydrazinium chloride in boiling acetic acid to afford 2-(indol-2-carboxamido)benzoic acids in good to excellent yields and 2-indolyl-3,1-benzoxazin-4-ones as by-products. The formation of the latter products could easily be suppressed by a hydrolytic workup. Alternatively, by increasing the reaction temperature and/or time, 2-indolyl-3,1-benzoxazin-4-ones can be obtained exclusively. Optimisations of the reaction conditions as well as the scope and the course of the transformations were investigated. The products were characterized by 1H, 13C and 15N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments (1H-1H gs-COSY, 1H-13C gs-HSQC, 1H-13C gs-HMBC) with 1H-15N gs-HMBC as a practical tool to determine 15N NMR chemical shifts at the natural abundance level of 15N isotope., TBU in Zlin [IGA/FT/2014/010]; Ministry of Education, Science and Sport, Republic of Slovenia; Slovenian Research Agency [P1-0230, 430-168/2013/114]; EN-FIST Centre of Excellence, Ljubljana

N-(α-Ketoacyl)anthranilic acids were prepared by oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones by using paraperiodic acid (H5IO6) or sodium periodate (NaIO4). The optimisation of the reaction conditions is described as well as the utilisation of N-(α-ketoacyl)anthranilic acids in the preparation of anthranilic acid hydrochlorides.

In the title hydrate, C(12)H(13)NO(4)·H(2)O, the piperidine ring that is fused to the benzene ring is in a sofa conformation with the chiral C atom lying 0.4084 (18) Å out of the plane of the nine fused-ring atoms. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules into chains running along the b-axis direction. The chains are further connected into layers parallel to the bc plane by π-π inter-actions between inversion-related benzene rings [centroid-centroid distance = 3.8846 (9) Å].

In the title compound, C12H13NO3, the quinoline ring system is approximately planar with a maximum deviation from the least-squares plane of 0.058(2)Å. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the molecules into chains running along the b-axis direction. The chains also feature π-π interactions between pyridine and benzene rings of inversion-related molecules [centroid-centroid distance = 3.609(2)Å]., TBU in Zlin - resources of specific university research [IGA/FT/2012/043]; Slovenian Research AgencySlovenian Research Agency - Slovenia [P1-0230-0103, BI-CZ/07-08-018]

The structure of the title compound, C(26)H(31)NO(12), contains an essentially planar quinoline skeleton, with the maximum deviation from the best plane being 0.055 (2) Å, and an oxane ring in a classical chair conformation with the following Cremer and Pople puckering parameters: Q = 0.586 (2) Å, θ = 11.5 (2)° and ϕ = 309.4 (10)°. One acetyl group displays rotational disorder with occupancies of 0.634 (8):0.366 (8). The crystal packing is stabilized by N-H⋯O hydrogen bonds, which link mol-ecules into chains along the a axis. The packing is further stabilized by weak C-H⋯O interactions. The absolute configurations on the carbons in the oxane ring correspond to those of the commercial starting material and are unchanged in the well known mechanism of the Koenigs-Knorr synthesis.

In the title compound, C16H13NO2, the quinoline system is approximately planar with a maximum deviation from the least-squares plane of 0.059 (1) Å for the N atom. The phenyl ring is rotated by 62.16 (4)° with respect to the plane of the quinoline system. In the crystal, O - H⋯O hydrogen bonds link molecules into infinite chains running along the b-axis direction., TBU in Zlin [IGA/FT/2012/043]; Slovenian Research AgencySlovenian Research Agency - Slovenia [P1-0230-0103, BI-CZ/0708-018]; EN-FIST Centre of Excellence, Ljubljana