Pharmaceutical Chemistry Journal (v.49, #5)

The Pharmacokinetics of Technetium-99m-Labeled N,N,N′,N′-Ethylenediaminetetra-Kis-(Methylenephosphonic Acid) in Intact Rats by V. M. Petriev; V. K. Tishchenko; K. V. Koptyaeva; O. A. Smoryzanova; V. G. Skvortsov (287-291).
Pharmacokinetic studies of technetium-99m-labeled N,N,N′,N′-ethylenediaminetetra-kis-(methylenephosphonic acid) (99mTc-EDTMP) showed that this radiopharmaceutical (RP) has high in vivo stability. Studies of the biodistribution of 99mTc-EDTMP were performed in healthy rats. Labeled agent was found to accumulate mainly in bone tissue. The greatest activity in the skeleton, (1.93 ± 0.12)%/g, was seen 1 h after i.v. administration. Accumulation of 99mTc-EDTMP content in the skeleton was 4.7 – 24.3 times greater than that of sodium pertechnetate (Na99mTcO4) (p < 0.001). Numerical values for differential accumulation coefficients (DAC) for activity in bones and internal organs and tissues were found to increase gradually to maximum values 3 h after i.v. administration. RP was eliminated mainly via the urinary tract. Study agent was rapidly cleared from the blood and only minor quantities accumulated in the internal organs. Contents were lower than those of Na99mTcO4 in in virtually all organs and tissues. These results indicate that 99mTc-EDTMP can be regarded as a potential RP for diagnostic investigations of bone tissues.
Keywords: N,N,N′,N′-ethylenediaminetetra-kis-(methylenephosphonic acid); EDTMP; technetium-99m; pharmacokinetics

Synthesis and Myelostimulatory Activity of a Number of 3,7-Diazabicyclo[3.3.1]Nonane Derivatives by K. D. Praliev; T. K. Iskakova; L. K. Baktybaeva; A. E. Malmakova (292-295).
Mannich condensation was used to synthesize new bispidinones, Wolff-Kishner reduction of which produced the corresponding bispidanes. 1H NMR spectroscopy studies showed that these existed in the double chair conformation. The myelostimulatory activity of the compounds synthesized here was assessed.
Keywords: bispidinones; 3,7-diazabicyclo[3.3.1]nonanes; β-cyclodextrin; myelostimulatory activity; immunostimulatory activity

Synthesis and Cytotoxic Activity of 1,2,3-Triazole Derivatives in Glioma Cell Cultures by I. S. Khazhieva; T. V. Glukhareva; O. S. El’tsov; Yu. Yu. Morzherin; A. A. Minin; V. A. Pozdina; M. V. Ulitko (296-300).
A series of 1,2,3-triazole derivatives was prepared and their cytotoxic actions on glioma cell cultures were studied. Amethod for the synthesis of 1-R-5-methyl- 1 H-[1,2,3]triazole-4-carboxamides is presented, based on transformation of 4-acetyl-1-phenyl- 1 H-[1,2,3]-triazolate sodium using primary amine hydrochlorides.
Keywords: 1,2,3-triazoles; diazo compounds; regrouping; biological activity; cytotoxicity; glioma; cell cultures; IC50

New (−)−Cytisine Derivatives with Nootropic Activity by N. S. Makara; S. F. Gabdrakhmanova; T. A. Sapozhnikova; R. Yu. Khisamutdinova; A. V. Koval’skaya; I. P. Tsypysheva; F. S. Zarudii (301-303).
The mnestic and antihypoxic effects of new derivatives of the quinolizidine alkaloid (−)-cytisine on acquisition of a conditioned passive avoidance reflex (CPAR) were studied in rats; effects on normobaric (jar) hypoxia were studied in mice. Screening studies showed that the benzamide and the N-(12-methylcytidin-3-yl)-N′-phenylurea not only improved learning and memory, but also increased the resistance of the brain to hypoxia.
Keywords: (−)-cytisine; nootropic activity; conditioned passive avoidance reflex; antihypoxic properties

N-Aroyl-α-aminoacrylic acid 2-(dialkylamino)alkylamides and their quaternary ammonium salts were synthesized and their physicochemical properties were determined. Results obtained from studies of their interactions with human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) are presented. IC50 values (concentrations producing 50% inhibition of the rate of cholinesterase hydrolysis of 0.1 mM acetylthiocholine) were determined for all the compounds synthesized. The results show that all the compounds synthesized had anticholinesterase properties, mainly specific in relation to BChE. Data on the antibacterial properties of the synthesized compounds are also presented.
Keywords: α-aminoacrylic acid derivatives; anticholinesterase properties; iodomethylates of dialkylaminoalkyl amides; AChE; BChE

Synthesis, Properties, and Biological Activities of 2-Methyl- and 2-Styrylquinoline-4-Carboxylic Acids by A. N. Dubrovin; A. I. Mikhalev; S. V. Ukhov; A. G. Goldshtein; V. V. Novikova; T. F. Odegova; R. R. Makhmudov (309-312).
Reaction of 2-methylquinoline-4-carboxylic acids with aromatic aldehydes in the presence of catalyst was performed to synthesize previously unknown 2-styrylquinoline-4-carboxylic acids. The structures of these compounds were verified using spectroscopic methods. Biological testing on animals showed that some of the resulting compounds had anti-inflammatory, analgesic, antimicrobial, and antifungal activity.
Keywords: 2-methylquinoline-4-carboxylic acids; 2-styrylquinoline-4-carboxylic acids; anti-inflammatory; analgesic; antimicrobial; antifungal activity

Synthesis and Biological Activity of 1-(4-Substituted Phenyl)-1-Alkyl(Aryl)-2-Phenyl-3-Aminopropan-1-Ol Hydrochlorides by N. K. Gasparyan; S. S. Mardanyan; I. G. Vermishyan; A. A. Antonyan; R. V. Paronikyan; G. A. Panosyan; G. A. Gevorgyan (313-318).
1-(4-Substituted phenyl)-2-phenylethanones were aminomethylated with paraformaldehyde and amine in ethanol to produce α-phenyl-β-amino-4-substituted propiophenones. Interaction of these with Grignard reagents in ether yielded tertiary aminopropan-1-ols and their hydrochlorides. Quite efficient inhibition, at differing levels, of adenosine deaminase (ADA, E.C. 3.5.44), one of the key enzymes in purine metabolism, by the compounds synthesized here was demonstrated. A structure-activity relationship was found for ADA inhibition. Most of the compounds synthesized here were found to lack antibacterial activity; only compounds Va, Vd, and VId displayed moderate levels of antibacterial activity against Gram-positive microorganisms.
Keywords: aminopropiophenones; aminomethylation; aminopropan-1-ols; adenosine deaminase (ADA) inhibitors

The activities of tannins from various plant extracts prepared by electroextraction were studied in a reaction with oxygen radicals during cathodic electroreduction of oxygen in an aqueous medium on a dropping mercury electrode. The value used for assessment of the antiradical activity of the study extracts was the parameter ∆φ – the displacement of the potential of the O2 electroreduction halfwave in the presence of extract as compared with the wave without extract. The greatest level of antiradical activity was seen with snakeweed and burnet root extracts, which have high contents of polymeric phenols. This method for assessing antiradical activity provides for a targeted approach to selecting tannin extracts as biologically active additives and as food antioxidants for dry products and liquid components such as syrups, vitamin juices, infusions, and purées.
Keywords: antiradical activity; plant extracts; tannins; antioxidants; cathodic electroreduction

A method for separating and assaying total free amino acids in aqueous extracts of medicinal plants by TLC was developed (using common sea buckthorn fruits and stinging nettle leaves as examples). The amino acid compositions of common sea buckthorn fruits and stinging nettle leaves were determined by capillary electrophoresis. An approach to assaying amino acids in a variety of objects is proposed, based on identification by determination of R s values without the use of standards. As the set of amino acids is individual for each type of plant material and depends on the means used for conservation, the chromatographic profile of amino acids can be used for standardization of materials.
Keywords: amino acids; common sea buckthorn fruits; stinging nettle leaves; thin layer chromatography; capillary electrophoresis

Technology and Standardization of Meadowsweet (Filipendula Ulmaria) Extract by I. V. Shilova; T. G. Khoruzhaya; I. A. Samylina (329-333).
The studies reported here led to proposal of an evidence-based technology for preparing liquid and dry extracts of meadowsweet (Filipendula ulmaria L.) using a multistage countercurrent extraction and contact drying process, and quality norms were established. Unified methods were developed for quality assessment (chromatography in thin layers of silica gel, UV spectroscopy) and assay (differential spectrophotometry using a state reference sample (SRS) of quercetin) of flavonoids in liquid and dry extracts of meadowsweet.
Keywords: flavonoids; extract; technology; standardization; Filipendula ulmaria (L) Maxim

A preparative method for a one-step synthesis of amino acid amides was developed using dimethyldichlorosilane. This method produces amides with yields ranging from 45% to 89% and purity greater than 95%. Neither racemization nor inversion of the configuration of the asymmetrical center in the starting α-amino acid occurs during the reaction.
Keywords: α-amino acids; amides; dimethyldichlorosilane; stereoselectivity

Manufacturing Requirements for Excipients Used in Medicines (Review) by M. M. Mironova; E. L. Kovaleva (340-343).
The level of production of an excipient is an important component in ensuring its quality. The quality assurance system for excipients for medicines in the Russian Federation does not fully meet current international requirements. We discuss here the questions of forming a systematic approach to assessing the production of excipients in international practice and the situation in the Russian Federation.
Keywords: excipients; good manufacturing practice (GMP) rules; medicines