R. G. Glushkov

Synthesis and pharmacological activity of derivatives of quinoline and condensed quinolines

It has been shown [i, 2] that alkylation products of derivatives of pyrrolo-, pyrido-, and azepino[2,3-b]quinolines possess neurotropic activity. In a continuation of this investigation, we have synthesized compounds of this type with a chlorine atom or a nitro group in position 6 of the quinoline ring, and we have examined the pharmacological properties of these compounds. The compounds were prepared by condensation of the esters of 5-chloro(or 5-nitro)anthranillc acid (la or b) with the diethyl acetals of dimethylacetamide (II), N-methyl-butyro-, -valero-, and-caprolactams (III), followed by intramolecular cyclization of the intermediate amidines and alkylation of the derivatives of quinolone-4 and the condensed quinolones (IV-VII) obtained with alkyl halides [3]. OH3

Chemistry of 3-nitroquinolines and their derivatives (review)

-Adrenoblockers (~-AB) are well established in contemporary medicine, constituting the principal group of drugs for the pharmacotherapy of common conditions of the cardiovascular system, namely ischemic cardiac disease, various forms of arterial hypertension, and arrhythmias [2, 7, i0, 12, 69, 90, 109, 145, 158, 179, 181, 196]. In addition, some novel applications of 8-AB in noncardiologial conditions have been identified, such as glaucoma, migraine, essential tremor, anxiety states, alcohol and narcotic withdrawal syndromes, thyrotoxicosis, hyperparathyroidism, and in obstetrics [4, 5, ii, 46, 80, 88, 91, 103, 124, 152, 165].

New potential antihypoxants based on 2-ethyl-3-(N,N-dimethylcarbamoyloxy)-6-methylpyridine

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.

New group of class III antiarrhythmic drugs: piperid-4-ylethane derivatives

It is established that succinic acid is capable of potentiating (synergism) the antihypoxic activity of 3-hydroxypyridine derivatives such as the succinate (Ia) and hydrochloride (Ib) of 3-(N,N-dimethylcarbamoyloxy)- 2-ethyl-6-methylpyridine. This effect makes it expedient to create new drugs containing a mixture of Ia or Ib and succinic acid derivatives that would possess antihypoxic, antiamnestic, and anticonvulsant activity. The antihypoxic activity of 3-hydroxypyridine drugs increases in the order emoxypin < mexidol < proxypin < Ia + succinic acid < Ib + succinic acid.

Synthesis and antifibrillatory activity of nibentan and its analogues

A series of new piperid-4-ylethane derivatives possessing antiarrhythmic activity has been synthesized and studied. The most active compound, 1-(4-fluorophenyl)-1-(4-nitrobenzoylamino)-2-(N-ethylpiperid-4-yl)ethane (niferidyl) hydrochloride, was selected for clinical trials as a potential class III antiarrhythmic drug.

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

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 biological study of pyracetam derivatives and related compounds

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.

Synthesis and biological activity of N-(β-arylethyl)amidines and N,N′-bis(β-arylethyl)amidines

In searching for new nootropic preparations we have carried out the synthesis and pharmacological study of a number of compounds obtained by modification of the pyracetam molecule. To achieve this modification in the present research we used methods that are widely employed in the chemistry of amides and lactams and are based on activation of their amide function by conversion to an amidoacetal function.

The original domestic drug oxolin: Refined structure of the drug and summarized experience of oxolin ointment use in medicine

The present work is devoted to the development of methods for synthesizing amidines having 6-arylethyl groupings attached to their N atoms, and to the study of their biological activity. It should be noted that amidines of this kind include a number of substances with biological activity [i, 2], including the coronary dilator mixidine, i.e., l-methyl-2-[6(3,4-dimethoxyphenyl)ethyl]iminopyrrolidine (I) [3, 4] OOH 3