Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives

A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro.It was found that most of the tested compounds especially compound 17, shown stronger activity to the selected three cell lines than ZM447439.     

Synthesis of pyrimido[4,5-b] indole derivatives

Chemistry of Heterocyclic Compounds -     

Glycolic acid-supported cobalt ferrite-catalyzed one-pot synthesis of pyrimido[4,5-b]quinoline and indenopyrido[2,3-d]pyrimidine derivatives

Herein, one-pot synthesis of pyrimido[4,5-b]quinoline and indenopyrido[2,3-d]pyrimidine derivatives was developed by the three-component reaction of aldehydes, 6-amino-1,3-dimethyluracil, and 1,3-dicarbonyl compounds in the presence of glycolic acid-supported cobalt ferrite CoFe₂O₄@SiO₂@Si (CH₂)₃NHCOOCH₂COOH as a novel magnetic catalyst in ethanol at reflux conditions. Glycolic acid-supported cobalt ferrite was characterized via Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and vibrating sample magnetometer (VSM). Moreover, the catalyst was easily recovered with magnetic separation and recycled at least for five times without significant loss of its catalytic activity. The products were formed in excellent yields over appropriate reaction times under environmentally friendly conditions. The high efficiency and easy isolation of catalyst from products with an external permanent magnet are some of the remarkable advantages of this method.     

异色满并[4,3-b]喹啉衍生物的合成

早在1931年,Hetherington等从念珠状曲菌(Aspergillus Cand inin)和土曲菌(Asperillus tereus)等菌类中分离出带有异色满(Isochroman)环系结构的左旋抗菌素橘霉素(C itrinin),后来又相继发现诸多带有异色满环系的天然产物[1-3],新近在软木木质素中也发现了多种具有异色满结构的     

New derivatives of 3-methylisoxazolo[5,4-b]pyridine

The synthesis and properties of 4,6-dichloro- (IV), 4-chloro- (XII) and 6-chloro-3-methyl-isoxazolo[5,4-b]pyridine (XI) are described. Depending on the reaction conditions compound IV with hydrazine or methoxide gave mono- or bi-substituted products. The halogen atom at the 4-position was shown to be the more mobile.     

Synthesis and properties of some pyrimido[5,4-d]pyrimidine derivatives

A method for the preparation of 2,4,8-trioxo-6-methyl derivatives of pyrimido[5,4-d]pyrimidine with various alkyl residues in the 7 position is described. It is shown that the chlorine in the 4 position of the 2,4-dichloro derivative of pyrimido[5,4-d]pyrimidine is the most labile in nucleophilic substitution reactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 517–520, April, 1977.     

An efficient synthesis of 3-aminoisothiazolo[5,4-b] -quinoline from quinoline

Treatment of readily available 3-formylquinoline-2-thiol ( 1 ) with ammoniacal sodium hypochlorite directly afforded isothiazolo[5,4-b]quinoline ( 3 ) in high yield, probably via 3-formylquinoline-2-sulfenamide ( 2 ). Facile conversion of 3 to the corresponding 3-amino derivative ( 7 ) was accomplished by the following sequence: base induced opening of the isothiazole ring to 3-cyanoquinoline-2-thiol ( 5 ), oxidation of 5 to the corresponding stable sulfenamide ( 6 ) and sodium ethoxide catalysed reclosure of the isothiazole ring which provided 3-aminoisothiazolo[5,4-b]quinoline ( 7 ).     

The synthesis of benzofuroquinolines. I. Some benzofuro[2,3-b]quinoline and benzofuro[3,2-c]quinoline derivatives

Benzofuro[2,3-b]quinoline ( Ia ) and its 11-methyl derivative ( Ib ) were synthesized by demethylcyclization of 3-(o-methoxyphenyl)-1,2-dihydroquinolin-2-ones (VIa,b). Benzofuro[2,3-b]quinoline-11-carboxylic acid (Id) was synthesized by chlorination followed by the action of potassium hydroxide of a lactone (IX) prepared by demethyl-cyclization of 3-(o-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-4-carboxylic acid (VIII). Isomeric benzofuro[3,2-c]quinoline (Ha) and its 6-methyl derivative (IIb) were synthesized by demethyl-cyclization of 3-(o-methoxyphenyl)-1,4-dihydroquinolin-4-ones (XIa,b). Both the methyl derivatives (Ib and IIb) were converted to the carboxylic acids (Id and IId) through condensation with benzaldehyde followed by oxidation. The benzofuroquinolines (Ia,b,d and IIa,b) thus obtained were oxidized to the corresponding N-oxides (IIIa,b,d and IVa,b).     

Study of the nucleophilic substitution reactions of 2,4,10-trichloropyrimido[5,4-b]quinoline

A number of pyrimido[5,4-b]quinoline derivatives were synthesized. It is shown that in the reaction of 2,4,10-trichloropyrimido[5,4-b]quinoline (II) with strong nucleophilic reagents (OCH₃ and SH) both of the halogens of the pyrimidine ring are replaced, while with amines substitution of the halogens of the pyrimidine ring proceeds successively; under more severe conditions, all three halogen atoms of II are replaced by amine residues.     

The synthesis of pyrimido[4,5-c]pyridazines and pyrimido[5,4-c]pyridazines

The Hofmann reaction on 6-methylpyridazine-3,4-dicarboxamide (1) gave a mixture of 3-methylpyrimido[4,5-c]pyridazine-5,7-dione (2), 3-methylpyrimido[5,4-c]pyridazine-6,8-dione (3) and an acid (4) of unknown structure. The Hofmann reaction on pyridazine-3,4-dicarboxamide (9) gave a mixture of pyrimido[4,5-c]pyridazine-5,7-dione ( 10 ) and an acid ( 11 ) of unknown structure. The reaction of 3-amino-6-methylpyridazine-4-carboxamide ( 18 ) with ethyl orthoformate gave 3-methylpyrimido[4,5-c]pyridazin-5-one ( 21 ). 4-Aminopyridazine-3-carboxamide ( 36 ) upon fusion with urea gave pyrimido[5,4-c]pyridazine-6,8-dione ( 37 ) while with ethyl orthoformate 36 gave pyrimido[5,4-c]pyridazin-8-one ( 38 ). Pyrimido[5,4-c]-pyridazine-8-thione ( 39 ) was obtained by the action of phosphorus pentasulfide on 38. 4-Amino-3-cyanopyridazine ( 16 ) when treated with formamide produced 8-aminopyrimido[5,4-c]-pyridazine ( 41 ). The synthesis of 4-aminopyridazine-3-carboxamide ( 36 ) and 4-amino-3-cyanopyridazine ( 16 ), both key intermediates in the synthesis of the novel pyrimido[5,4-c]pyridazine ring system was accomplished by the Reissert reaction of 4-aminopyridazine-2-oxides and subsequent conversion of the nitrile to the amide.     

Synthesis of isoxazolo[5,4-b]pyridine derivatives (microreview)

Chemistry of Heterocyclic Compounds - The microreview summarizes the data on heterocyclization methods leading to the formation of isoxazolo[5,4-b]-pyridines published over the last 5 years. The...     

Green synthetic approach toward new chromeno[4,3-b]quinoline and chromeno[4,3-b]pyridine derivatives

Chemistry of Heterocyclic Compounds - A facile, convenient, and efficient synthesis of new chromeno[4,3-b]quinoline and chromeno[4,3-b]pyridine derivatives has been accomplished via one-pot...     

Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a]quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives

A series of unusual fused heterocyclic compound derivatives, consisting of a pyridine and a imidazole or pyrimidine core, with a bridgehead nitrogen, were successfully synthesized by a microwave-assisted, three-component domino reaction of aldehydes, enaminones, and malononnitrile. In this one-pot reaction, up to five new bonds were formed accompanied by generating the lactam group. This method has the advantages of short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environment impact.     

Synthesis of 3-amino-5H-pyrimido[5,4-b]indol-4-one derivatives

Starting with ethyl 3-aminoindole-2-carboxylate, the synthesis of 3-amino-5H-pyrimido[5,4-b]indole-2,4-dione 5 , 3-amino-5H-pyrimido[5,4-b]indol-4-one 10 and some related compounds is described. Preliminary results about the inhibition of platelet aggregation by these compounds is reported.     

Optical absorption of 1H-pyrazolo[3,4-b]quinoline and its derivatives

The results of experimental studies and quantum chemical simulations of the absorption spectra of 1H-pyrazolo[3,4-b]quinoline and its derivatives are presented. The quantum chemical calculations (semi-empirical AM1 and PM3 methods) show similarity in the absorption spectra of 1H-pyrazolo[3,4-b]quinoline and 1,3-dimethyl-1H-pyrazolo[3,4-b]quinoline which are characterized by five strong absorption bands in the spectral range 200-500 nm. A substitution of the methyl groups by at least one phenyl group causes the drastic changes of the absorption spectra mainly within the spectral range 240-370 nm. We attribute these differences to additional molecular double bonding segments C=C of the substituted phenyl groups, i.e. to pi --> pi* transitions. A comparison of measured and the calculated absorption spectra manifests quite satisfactory agreement for all compounds in the part regarding the spectral position of the first oscillator (absorption threshold). At the same time, the measured spectra demonstrate the considerable broadening practically of all absorption bands and even complete damping some of them in the case of phenyl derivatives. The experiments performed with highly and weakly polar organic solvents shows that the solvent effect on the absorption spectra is small. For this reason the discrepancies between the calculated and the measured spectra are attributed to electron-vibronic coupling as well as to rotational dynamics of phenyl rings.     

Novel synthesis of isoxazolo[5,4-b]quinolines

Isoxazolo[5,4-b]quinolines have been prepared by reacting 3-acyl or aroyl-2-chloro-6-alkoxy or 6,7-dialkoxyquinolines with hydroxylamine. The method is of general applicability for obtaining this class of compounds and involves the use of easily available starting materials.