Pharmaceutical Chemistry Journal (v.43, #7)

Preclinical study of the α2-adrenostimulant Brimozolin (brimonidine) by V. N. Ermakova; G. P. Zakharova; G. V. Rybko (375-377).
A preclinical study of the α2 -adrenostimulant Brimozolin (brimonidine tartrate), synthesized by an original method at OAO Center for the Chemistry of Therapeutic Agents_All-Russian Chemico-Pharmaceutical Research Institute (TsKhLS-VNIKhFI), was performed using 29 rabbits. Brimozolin eye drops decreased intraocular pressure in the intact eyes of experimental animals by 3 – 5 mmHg for one day by producing significant increases in the outflow of aqueous humor and suppressing its production. Histological studies of the outer and inner layers of the eye showed that there were no changes. This agent is recommended for clinical trials.
Keywords: Specific activity; chronic toxicity; intraocular pressure; hydrodynamic parameters; histological studies

Effects of lupane and oleanane β-enaminoketones on the number and morphology of white blood cells by L. V. Anikina; I. A. Tolmacheva; Yu. B. Vikharev; V. V. Grishko (378-380).
The biological activity of several lupane and oleanane β-enaminoketones was studied. Comparative analysis of leukocyte reactions showed that both groups of triterpene derivatives had high biological activity on chronic administration and that their immunosuppressive activity resulted from toxic effects on lymphocytes.
Keywords: Triterpenoids; betulin; β-enaminoketones; leukocytes

Interaction of 6-methyl-2-chloro-3-cyano-5-ethoxycarbonylpyridine with potassium salts of amino acids was shown to form N-(6-methyl-3-cyano-5-ethoxycarbonyl-2-pyridyl)aminoalkanecarboxylic acids. Most of the resulting substances had procoagulatory activity.
Keywords: Synthesis; N-(2-pyridyl)aminoalkanecarboxylic acid derivatives; hemostatic activity

Synthesis of new hetero- and carbocyclic aromatic amides of glycyrrhizic acid as potential anti-HIV agents by R. M. Kondratenko; L. A. Baltina; L. A. Baltina. Jr.; O. A. Plyasunova; A. G. Pokrovskii; G. A. Tolstikov (383-388).
Members of a new group of di- and trisubstituted amides of glycyrrhizic acid (GA), the major component of licorice root extract, were synthesized; derivatives contained fragments of heterocyclic and aromatic amines (2-aminopyridine, 4-aminopyridine, 5-aminouracil, sulfadimezine, sulfapyridazine, and L-histidine methyl ester) using the dicyclohexylcarbodiimide method. Amides of GA containing 2-aminopyridine and 5-aminopurine residues had anti-HIV-1 activity in MT-4 cell cultures. The index of selectivity (IS) of the amide of GA with 5-aminouracil was, using various parameters, from 27.73 to 277.32, exceeding values for GA (from 4.45 to 24.0).
Keywords: Glycyrrhizic acid; hetero- and carbocyclic amides; synthesis; anti-HIV activity

Synthesis and pharmacological activity of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides by N. K. Gasparyan; R. G. Paronikyan; A. E. Tumadzhyan; A. A. Tatevosyan; G. A. Panosyan; G. A. Gevorgyan (389-392).
Aminomethylation of substituted acetophenones with paraformaldehyde and piperidine hydrochloride yielded 4-substituted β-piperidinopropiophenones. Interaction of compounds I with the Grignard reagents in ether yielded 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanols. The anti-inflammatory, analgesic, antipyretic, central m-cholinoblocking, and peripheral n-cholinoblocking actions of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides were studied. The study compounds were found to have marked central m-cholinoblocking and peripheral n-cholinoblocking activities. Only 1-(4-methoxyphenyl)-1-cyclohexyl-3-piperidinopropanol hydrochloride had anti-inflammatory activity.
Keywords: β-Piperidinopropiophenones; aminomethylation reaction; 3-piperidinopropanols; anti-inflammatory; analgesic; antipyretic; central m-cholinoblocking; and peripheral n-cholinoblocking activity

Interaction of substituted 4-acylpyrrolin-2-ones with primary amines and the antimicrobial activity of the resulting compounds by V. L. Gein; V. A. Mikhalev; É. V. Voronina; M. I. Vakhrin; E. B. Babushkina (393-395).
Interaction of 1-(2-methoxyethyl)-5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones with aromatic amines such as p-toluidine, p-bromaniline, and p-anisidine and aliphatic amines such as butylamine and ethanolamine formed 5-aryl-4-aroyl-3-arylamino-1-(2-methoxyethyl)-3-pyrrolin-2-ones and 4-(1-R2-aminoethylene)-tetrahydropyrrol-2,3-diones. The antimicrobial activities of the resulting compounds were studied.
Keywords: Substituted 4-acylpyrrolin-2-ones; antimicrobial activity

Synthesis and antimicrobial and antifungal activities of compounds of the naphthazarin series by A. Ya. Yakubovskaya; N. D. Pokhilo; V. F. Anufriev; M. M. Anisimov (396-398).
A series of substituted naphthazarins (5,8-dihydroxy-1,4-naphthoquinones) were synthesized and their antimicrobial and antifungal activities were studied. The yeast Saccharomyces carlsbergensis was the most sensitive to these compounds. Among the compounds studied, the most marked antimicrobial and antifungal activities were obtained with unsubstituted naphthazarin, which was as active as juglone.
Keywords: 5,8-Dihydroxy-1,4-naphthoquinone; naphthazarin; antimicrobial activity; Saccharomyces carlsbergensis ; Staphylococcus aureus ; Escherichia coli

A method for the selective assay of isoflavonoids, flavonoids, and phenolcarboxylic acids in the field restharrow was developed using a combination of differential direct spectroscopy and the additivity principle; the method was validated. This method can be used for standardization and assessment of the quality of raw material in terms of active substances.
Keywords: Field restharrow; standardization; spectrophotometry

The degradation products of proanthocyanidines of root rhizomes of the marsh cinquefoil were studied. The anthocyanidine extracted was identified as cyanidine chloride using chromatographic and UV spectrophotometric methods.
Keywords: Marsh cinquefoil; chromatography; UV spectrophotometry; proanthocyanidine

Physicochemical parameters of perfluorocarbon emulsions with different osmolarities by I. N. Kuznetsova; V. S. Yurchenko; G. A. Kochetkova (408-414).
The physicochemical properties of emulsions based on perfluorocarbons (PFC) and phospholipids (PL) with osmolarities from ~80 to ~230 mOsm were studied in conditions of normal storage at +4°C and in “accelerated aging” storage at +37°C. Heat sterilization of emulsions with osmolarities of ~80 mOsm had no effect on particle size or structure. The pH and structure of these media remained unchanged for 12 months of normal storage. Increases in the osmolarity to ~230 mOsm had no effect on the stability of the emulsions: particle size and structure and pH and viscosity remained unaltered for 30 – 40 days of “accelerated aging” or for a year in normal (+4°C) conditions.
Keywords: Emulsion; perfluorocarbons; phospholipids; osmolarity; stability (+4°C)

The optimum conditions for separating a lignan-containing extract from seeds of the oil flax (Linum usitatissimum) by thin-layer chromatography were identified. Elution using the method proposed here allowed identification of a brilliant blue fluorescent spot associated with the main lignan, which was secoisolariciresinol diglucoside (SDG), giving clear identification of this component in mixtures even without a standard. This method can be used for qualitative express analysis of phytopreparations based on lignans, with the aim of detecting adulterated phytopreparations and biologically active additives.
Keywords: Oil flax seeds; lignan-containing extract; separation

Comparative IR spectral characteristics of humic acids from peats of different origin in the Tomsk area by M. V. Gostishcheva; M. V. Belousov; M. S. Yusubov; R. R. Ismatova; S. E. Dmitruk (418-421).
Results obtained from comparative studies of the structures of humic acids from peats of different origins in the Tomsk area by infrared spectroscopy are presented. These data showed that the IR spectra of humic acids extracted from different types of peat had high levels of similarity, demonstrating similarities in their chemical structures. Humic acid from lowland woody-grassy peat had very significant differences from other types of peat and consisted of compounds with high proportions of aliphatic fragments and, perhaps, lower benzenoid levels, as well as higher contents of active acid groups (carboxyl, hydroxyl).
Keywords: Humic acids; peat; IR spectra

Application of low-angle laser scattering to the quality control of pharmaceutical powders and suspensions. 2. Barium sulfate by A. S. Ul’yantsev; E. V. Uspenskaya; N. S. Sorokina; T. V. Pleteneva; A. V. Syroeshkin (422-424).
Low-angle light scattering was used for dispersion analysis of samples of barium sulfate substance for radiography obtained from various manufacturers. Particles with sizes of greater than 10 μm were detected, which is not in compliance with normative specifications. Results obtained using barium sulfate substance as an example allow the low-angle laser light scattering method to be recommended for the rapid control of particle size in the disperse phases of medicinal suspensions and powders.
Keywords: Powders and suspensions; barium sulfate; dispersion analysis; low-angle laser light scattering

Analysis of ranitidine hydrochloride by near IR spectroscopy by E. V. Stepanova; A. P. Arzamastsev; A. V. Titova (425-427).
IR spectroscopy in the near infrared range is a new method recently introduced into the practice of pharmaceutical analysis. The present report shows that this method can be used to confirm the identity of ranitidine hydrochloride substance and to identify tablet manufacturers.
Keywords: Ranitidine hydrochloride; substance; tablets; near IR spectroscopy; discriminant analysis

An ion-selective sensor for assay of diclofenac in medicines by Zh. A. Kormosh; I. P. Hunka; Y. R. Bazel (428-430).
A diclofenac-selective electrode with a plasticized polyvinylchloride membrane was developed. The electrode contained an ionic associate of diclofenac with neutral red and its response was linear over the diclofenac concentration range 5 × 10–5 to 5 × 10–2 M with an electrode function slope of (30.0 ± 1.1) - (44.0 ± 1.2) mV/pC. This membrane electrode was used as a sensor for assaying diclofenac in pharmaceutical formulations.
Keywords: Diclofenac sodium; selective electrode; polyvinylchloride membrane