4-Hydroxy-2-quinolones. 154*. Pyrimidin- 2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydro- quinoline-3-carboxylic acids. synthesis, structure, and properties

Abstract

Keywords: 2-aminopyrimidine, 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides, bromination, antitubercular activity, X-ray structural analysis.Pyrimidine bases occur in a number of the most widespread heterocyclic systems in nature. Occurring in nucleic acids and coenzymes these compounds play a direct role in encoding and transmitting hereditary information, in the metabolism of carbohydrates and lecithin, and also in many biochemical processes important for animals and plants [2]. As a result, natural pyrimidines have an extremely broad spectrum of biological activities: from vitamins and regulators of biosynthesis amongst specific living organism proteins to antibiotics and alkaloids and to tetrodotoxin [3] which is one of the most powerful non-protein neurotoxins. Of course, pharmaceutical chemistry has not stood aside from the facts listed. As a result, to this day around 100 synthetic preparations [4] based on pyrimidine have been created and indeed used in medicinal practice. The majority of them fit into four broad categories of well known substances: barbiturates, sulfanilamides, antimicrobial pyrimidine-2,4-diamines, and antitumor agents [3]. Less impressive but none the less valuable for public health are such pharmacological groups as diuretics, antihypertensive and antihistamine agents, anticonvulsants, vitamins etc. [3,4].

4-Hydroxy-2-quinolones. 168*. Synthesis, chemical and antitubercular properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides

“…However, the pyrazine fragment unexpectedly shows only two singlets of one proton (H-3) and two protons (H-5 and H-6) where in the latter case the signals at least for H-5 and H-6 should be observed as two separate doublets with a characteristically small α-pyridine type vicinal spin-spin coupling. Similarly to the 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrimidin-2-ylamides we have previously reported [18], treatment of pyrazin-2-ylamides 1 with saturated 1-N-alkyl substituents in glacial acetic acid medium with molecular bromine gives light-orange crystalline precipitates which are evidently the perbromides 3a-m. 2-Aminopyrazines can be halogenated in the para position to the amino group [19] so subsequent refluxing of the reaction mixture (as in the case of the pyrimidin-2-ylamides [18]) would logically be expected to brominate the amide part of the molecule, i.e. to convert the perbromides 3a-m to the 5-bromopyrazin-2-ylamides of the corresponding quinoline-3-carboxylic acids.…”

“…It should be noted here that the 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid hetarylamides do not survive gas column chromatography without destruction hence we could not carry out the corresponding chromato-mass spectrometric analysis. As is known, under electron impact ionization the primary degradation of the molecular ions for this type of compounds occurs via a ketene [18]. In the example we are discussing, this behavior is retained but the bromine is found exclusively in the ketene fragment 6b with m/z 293/295.…”

“…The lower the shift of the proton signal the greater the electron density on the carbon atom bonded to it. From the information in the scheme below it is seen that the least shift (7.28 ppm) seen in the 1-butyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrimidin-2-ylamide (8) is for the pyrimidine H-5 proton and it is known, in fact, that bromination occurs at this position [18]. In the case of the isomeric pyrazin-2-ylamide 1f the picture is very different.…”

4-hydroxy-2-quinolones. 191.* synthesis, tautomerism and biological activity of benzimidazol-2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids

“…However, on the other hand, a monocrystal of the amido ester was grown from solution, which proved suitable for X-ray diffraction crystallographic structural analysis, and important information was obtained on the three-dimensional study of this class of compounds. As expected, many specific structural features were found common for primary N-R-amides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids [26][27][28]. Thus, in particular, amido ester 4 gives rise to an analogous system with strong intramolecular hydrogen bonds: 4-OH···O=C-NH and 6-C=O···HNC=O, which accounts for the existence of only the amide tautomer in the crystal, while the pyridine ring, carbamide group, and benzimidazole fragment lie in a single plane.…”

“…Comparing the data for preliminary screening (Table 3) with the results of a study of the antituberculosis properties for others diazahetarylamides of 1-R-4-hydroxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acids, we found that the benzimidazole derivatives had significantly higher activity than compared to pyrimidine analogs [28]. On the other hand, our products were inferior to pyrazin-2-ylamides [31] both in their capacity to repress the growth of a test strain and relative to the minimal inhibiting concentration (MIC) determined only for the most active samples.…”