N. K. Davydova

Chemistry of 3-nitroquinolines and their derivatives (review)

Interest in the nitro derivatives of heterocycles, and particularly nitroquinolines, as the source of potential drug preparations is determined by the high biological activity of drugs of this group of compounds: 5-NOX (nitroksalin) and metronidazole. From this veiwpoint, special attention is merited by derivatives of 3-nitroquinoline, particularly 1-substituted 3-nitro-4-oxo-l,4-dihydroquinolines, as structural analogs of preparations of the 4-quinolone-3-carboxylic acid group [i, 2], possessing a broad spectrum of antibacterial action.

Synthesis and antifibrillatory activity of nibentan and its analogues

A series of 1,5-diaminopentane derivatives, structurally related to nibentan, was synthesized and tested for antifibrillatory activity. Improved modifications of some known chemical syntheses were proposed. (+/-)-N-[5-(Diethylamino)-1-(4-nitrophenyl)pentyl]-benzamide hydrochloride, (+/-)-N-[5-(diethylamino)-1-(4-nitrophenyl)pentyl]-4-nitrobenzamide hydrochloride and (+/-)-N-[5-(diethylamino)-1-(4-hydroxyphenyl)pentyl]-4-nitrobenzamide hydrochloride were more potent than nibentan and possessed a longer duration of action (up to 5 h in comparison with 60-90 min for nibentan). The antifibrillatory activity of (+/-)-N-[5-(diethylamino)-1-(4-methoxyphenyl)pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-sotalol and sematilide.

Synthesis and antiprotozoal activity of some N-alkyl-3-nitroquinolones-4

By alkylating the sodium salt of 2-methyl-3-nitroquinolone-4 (IIIa) with EtI in DMF we isolated l-ethyl-2-methyl-3-nitro-4-oxo-l,4-dihydroquinoline (Ia). 1-Methyl substituted 3-nitroquinolones-4 II were prepared by treating 3-nitro-4-oxo-l,4-dihydroquinolines III with dimethyl sulfate or methyl p-toluenesulfonate in the presence of a phase-transfer catalyst tetrabutylammonium chloride in the heterogeneous system consisting of aqueous NaOH solution and chlorobenzene.

Use of the Koch-Haaf reaction in a new synthesis of gemfibrozil

The Koch-Haaf reaction (carbonylation of alcohols or alkenes with carbon monoxide in a highly acidic medium) is a well-known and convenient method for synthesizing tertiary carboxylic acids under mild conditions. However, it has failed to find favor for aromatic compounds because the intermediate carbocation formed as a result of the rearrangement yields a mixture of complicated products. Only Takahashi, et al., [1] have described the preparation ofdiarylacetic and diarylpropionic acids under conditions of the Koch-Haaf reaction, from the corresponding diarylmethanol and diarylethanol. We studied the possibility of using the Koch-Haaf reaction in the synthesis of gemfibrozil [2,2-dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid] (I), a valuable drug used for prophylaxis and treatment of atherosclerosis [2]. We prepared acid I both from an alcohol (II) and from an alkene (III). In both cases, the reaction proceeds via an intermediate carbocation (IV) that forms in a highly acidic medium (98% H2SO4). Carbocation IV reacts with the carbon monoxide generated from formic acid and transforms into carbocation V, whose hydrolysis facilitates the formation of acid I. We have shown that depending on the selected conditions, different compounds can be obtained in this reaction. For example, when it is conducted in concentrated sulfuric and formic acids, acid I and a formyl derivative (VI) form in the ratio 3 : 1. The structure of the compounds is confirmed by mass and PMR spectra. In the mass spectrum of gemfibrozil I, the relevant molecular peak ion is observed with a

Synthesis and alkylation of 9-ethoxy-1H-pyrrolo[3,2-b]quinoline

Abstract9-Ethoxy-1H-pyrrolo[3,2-b]quinoline has been synthesized by the hydrogenation of 2-[2-(N,N-dimethylamino)vinyl]-3-nitro-4-ethoxyquinoline using Raney nickel. Alkylation using N,N-dimethylchloroethylamine and hydrolysis with HBr gave two isomers whose structures were established using PMR and mass spectrometry.

Synthesis of 4-methyl-1H-imidazo[4,5-c]quinoline

A four-step synthesis of 4-methyl-1H-imidazo[4,5-c]quinoline from 2-methyl-3-nitro-4-oxo-1,4-dihydroquinoline is developed.