L. Yu. Krylova

Synthesis and biological activity of 7,8-polymethylenepurines

This report is a continuation of our studies on the synthesis of 7,8-polymethylene derivatives of purine and the systematic search for biologically active substances among these compounds. The synthesis and biological activity of the isomeric 8,9-polymethylenepurines have been studied in detail [2]. However, purine derivatives containing polyethylene chain in position 7 and 8 have received very little study [5].

Experimental Evaluation of the Chemotherapeutic Efficacy and Toxicity of a New Medicinal Form of Dioxidine: Lidoxycol Ointment

The antibacterial activity in vitro and in vivo and the toxicity of Lidoxycol ointment, which is a new medicinal form of dioxidine, have been studied in comparison to the properties of Dioxycol ointment. The results showed that Lidoxycol is identical to Dioxycol with respect to the spectrum of antimicrobial action, chemotherapeutic efficiency, and tolerance.

Synthesis and Antituberculous Activity in vitro of Amidine and Hydrazidine Analogs of Pyrazinamide and Isoniazid

This study was aimed at modification of the structures of pyrazinamide and isoniazid by substituting amidine and hydrazidine instead of amide and hydrazide moieties. The target compounds are of independent basic interest and can be used as prodrugs. In the first stage, pyrazinocarboxylic (I) and isonicotinic (V) acid amides were converted into the corresponding nitriles (II, VI). Using conventional methods [1 – 3], these nitriles were converted into hydrochlorides of the corresponding iminoesters (III, VII) and amidines (IV, VIII) (Schemes 1 and 2).

Checking the Efficacy of a New Original Biological Probe for Steam Sterilization of Nutrient Media and Solutions

Requirements on the reliability of sterilization processes are increasing throughout the world. This is confirmed by the fact that a series of important international, European, and national standards concerning sterilization were introduced in recent years. The GMP Rules adopted by the European Economic Community stipulate using, besides other, biological methods for the sterilization process control. Russia is not an exception: a special technical committee engaged in the sterilization problems was established at the State Committee of Standardization of the Russian Federation. The first State Standards developed and accepted in 1997 – 1999 were concerned with the problems of control of sterilization processes [1 – 5]. The chapter on “Sterilization” of the State Pharmacopoeia stipulates that the parameters and efficacy of thermal sterilization methods have to be monitored with the aid of special measuring instruments and by chemical and biological probes. However, normative and technological documentation of pharmaceutical enterprises contain no requirements concerning biological control. In recent years, biological methods for monitoring the sterilization of medicinal articles have been implemented into the practice of medical, sanitary-and-prophylactic, and pharmaceutical institutions. However, such methods are not used to monitor the regime of sterilization of drug solutions and nutrient media, although such processing of solutions is a necessary stage of many technological processes. Instrumental techniques are used to measure certain physical parameters of the sterilization process (temperature, time, pressure); using chemical methods, it is possible to judge on one or several characteristics of the process; but only biological methods allow the total influence of all factors on the results of sterilization treatment to be evaluated [6 – 8]. The essence of biological methods consists in using biological probes, representing standard preparations of certain microorganisms, for evaluating the efficacy of the sterilization process [6]. A typical preparation contains the spores of Bacillus stearothermophilus in a special nutrient medium which acquires a yellow color in the presence of growing spores. The purpose of this work was to develop a domestic sterilization bioprobe and check for its applicability as a means of monitoring the efficacy of a steam sterilization process.

SYNTHESIS AND ANTIVIRAL ACTIVITY OF 2-PHENOXYMETHYL DERIVATIVES OF 5-HYDROXYINDOLE

As starting compound, we used the previously described l-methyl-2-bromomethyl-3-ethoxycarbonyl-5-acetoxy-6-bromoindole (I). When this was reacted in acetone with phenols and phenolamines containing methyl, bromo, or nitro groups at position 4, 2-phenoxymethyl derivatives of 5-acetoxyindole (II-V) were obtained. When unsubstituted phenol was used, we isolated •-methy•-2-phen•xy-3-eth•xycarb•ny•-5-(•-methy•-3-eth••ycarb•ny•-5-acet•xy-6-br•m•indolyl-2-methoxy)-6-bromoindole (VI) as a by-product. Carrying out the same reaction in aqueous dioxane in the presence of KOH leads to O-deacylation, shown by reacting 5-acetoxyindole (I) with 4-methoxyphenol, which resulted in the isolation of the 5-hydroxyindole derivative (X). Alkaline hydrolysis of 5-acetoxyindoles II-V gave the corresponding 5-hydroxyindoles VII-X.

Aminoalkyl-5- and -6-hydroxyindoles and their antiviral activity

Bromination of (VII) with N-bromosuccinimide (NBS) in CC14 with illumination in the presence of benzoyl peroxide afforded l-phenyl-2-bromomethyl-3-ethoxy-carbonyl-6-acetoxyindole (VIII) o In the PMR spectrum of this compound, the position and multiplicity of the signals for the aromatic protons were similar to those for the same protons in the starting material (VII), and in addition a singlet signal was present at 6 = 4.93 ppm attributable to the protons of the methylene group in the 2-position of the indole ring. However, bromination of (VII) with bromine in acetic acid gave (IX), the PMR spectrum of which as compared with that of (VII) contained a singlet signal for the 2-methyl group at 2.53 ppm, signals for the protons in positions 4 and 7 with characteristic multiplicity, but no signal for a proton in the 5-position. Bromination of (VIII) with bromine in acetic acid gave the dibromide (X), which was also obtained by boiling (IX) with NBS in CCI~ with illumination in the presence of benzoyl peroxide. Reaction of (X) with thiophenol in alcohol in the presence of KOH gave the 2-phenylthiomethyl derivative of 6-hydroxyindole (XI), which on reaction with bis(dimethylamino)methane was converted into (XII).

Synthesis and antiviral activity of 5-oxyindole derivatives

We had assumed that the 3-acetyl-5-acetoxyindoles (I, II) would be brominated by N-bromosuccinimide (NBS) in CCI~ at position 6 of the benzene ring in the same way that derivatives of 3-ethoxycarbonyl-5-acetoxy(methoxy)indole are brominated [4]. However, judging by the PMR spectra, substitution took place in the CH~ group at C(=) which confirms the presence of CH2Br group proton signals (5 4.99 ppm) at C(2 ) . The PMR spectrum also has proton signals at positions 4, 6, and 7 with their characteristic multiplet property.

Investigation of antiviral activity among derivatives of 4-oxybenzofuran

In that connection we obtained derivatives of 4-oxybenzofuran with acetylaminomethyl substituents in position 3 of the benzofuran ring. The starting compounds were Mannich bases la-d [3] which were then subjected to acetylation, O-alkylation, and hydrolysis. We obtained the amides lla-d from the amines la-d through the action of acetic anhydride at 20*C. This reaction resulted in a high yield of the target compounds (75-93%) and there was no observed formation of O-acylation products under these conditions.