Pharmaceutical Chemistry Journal (v.45, #4)

Comparative analysis of the experimental and clinical pharmacokinetics of Amiodarone by V. G. Kukes; S. N. Kondratenko; A. K. Starodubtsev; V. V. Chistyakov; T. A. Posrednikova (199-202).
The pharmacokinetics of two tablet formulations of amiodarone – Amiodarone and Amiodaron-Akri – were studied in 12 rabbits and 18 healthy human volunteers after single p.o. doses of 200 mg. A highly statistically significant correlation was found between plasma amiodarone concentrations in rabbits and volunteers (r = 0.8263, p < 0.001). Normalized C max and AUC 0−∞ values were significantly greater in volunteers than rabbits, while specific V Z and Cl t values were lower and MRT was significantly higher; rate coefficients of absorption and measures of relative bioavailability showed no statistically significant differences between rabbits and healthy humans.
Keywords: Amiodarone; pharmacokinetics; plasma concentrations; relative bioavailability; rabbits; healthy volunteers

Studies of parmidine metabolism by A. S. Berlyand; A. A. Prokopov (203-204).
The metabolism of parmidine, an angioprotector with marked antisclerotic actions, was studied in humans. The main direction of this process was sequential demethylation. After p.o. administration, parmidine was excreted from the human body as two metabolites – the monodemethyl- and didemethylpyridinolcarmabates. The structures of these metabolites were confirmed by direct synthesis.
Keywords: Parmidine; metabolism; demethylation

A potential combined formulation containing vinpocetin and succinic acid by R. G. Glushkov; S. D. Yuzhakov; N. I. Andreeva; M. V. Alekseev; V. V. Asnina; E. N. Salin (205-207).
Succinic acid bas been found to be able to potentiate the antihypoxic activity of vinpocetin. This property (potentiation) provided grounds for creating a new combined formulation containing vinpocetin and succinic acid, which has more marked antihypoxic activity than the initial single-substance vinpocetin formulation, along with antiamnestic and anticonvulsive activities.
Keywords: Vinpocetin; succinic acid; antihypoxic activity; synergism

Synthesis and antitumor activity of fluorinated derivatives of [i,j]-annelated quinolones by G. N. Lipunova; É. V. Nosova; L. P. Sidorova; V. N. Charushin (208-210).
Tri- and pentacyclic fluoroquinolones were synthesized by intramolecular cyclization of the corresponding 3-hydrazinopolyfluorobenzoylacrylates followed by substitution of fluorine atoms by amine residues. The antitumor activity of the resulting compounds was studied at the National Cancer Institute using cultures of 60 cell lines of nine groups, including leukemia, lung tumor, large intestine tumor, CNS tumor, melanoma, ovary tumor, renal tumor, prostate tumor, and breast tumor. Relationships between structure and antitumor activity were analyzed. In vivo experimental data from hollow fiber tests are presented for two derivatives.
Keywords: 1,3,4-Thiadiazino[5,6,4-i,j]quinoline; benzimidazo[2′,3′:3,4]-1,2,4-triazino[5,6,1-i,j]quinoline; synthesis; antitumor activity

Synthesis and antitumor activity of a series of benzofuryl-substituted 1,2,4-triazoles and triazolin-5-thiones by M. A. Kaldrikyan; L. A. Grigoryan; R. G. Melik-Ogandzhanyan; F. G. Arsenyan (211-214).
3-Benzofuryl-4-benzyl(cyclohexyl)-5-mercapto-1,2,4-triazoles were synthesized by cyclization of the corresponding substituted thiosemicarbazides. 5-Mercaptotriazoles were S-alkylated with various alkenyl-substituted benzylhalogenides, chloracetamide, chloroacetic, and α-bromopropionic and α-bromocaproic acids. The aminomethylation and hydroxymethylation reactions of 3-benzofuryl-4-benzyl(cyclohexyl)-5-mercapto-1,2,4-triazoles were studied. The antitumor activity of the resulting compounds was investigated.
Keywords: Thiosemicarbazide; hydrazide; mercaptotriazole; S-alkylation; N-aminomethylation; triazolin-5-thiones

Synthesis and neurotropic properties of arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones by S. A. Andronati; T. L. Karaseva; A. A. Kazakova; V. I. Pavlovskii; S. Yu. Bachinskii (215-216).
The neurotropic properties (antidepressant, sedative, anticonvulsant) of new 3-arylidene derivatives of 1,2-dihydro-3H-1,4-benzodiazepin-2-one were studied. A number of the study compounds were found to have high levels of antidepressant activity and the nature and position of the substituents in the phenyl radical and the arylidene fragment of the molecule were found to have significant influences on their antidepressant properties.
Keywords: Neurotropic properties; benzodiazepines; antidepressant activity

Synthesis and antituberculous activity of quinoline isosteres of isoniazid by A. V. Zimichev; M. N. Zemtsova; A. G. Kashaev; Yu. N. Klimochkin (217-219).
We present an evaluation of the antimycobacterial activity of a series of 2-aryl(heteryl)-4-quinolinecarboxylic acids. Compounds with potential value against Mycobacterium tuberculosis H37Rv were found.
Keywords: 2-R-6-R′-4-Quinolinecarboxylic acids; 2-R-6-R′-4-quinolinecarboxylic acid hydrazides; tuberculosis

Free radical copolymerization was used to prepare copolymers of new structural types on the basis of azanorbornenes, 2,2-diallyl-1,1,3,3-tetraethylguanidinium chloride, and tris(diethylamino)diallylaminophosphonium salts with sulfur dioxide, two vinyl monomers, and maleimides. Two methods were used to assess the antioxidant activity of the resulting copolymers.
Keywords: Free radical copolymerization; azanorbornenes; diallyl monomers; antioxidants; erythrocyte hemolysis; lipid peroxidation

Synthesis and biological properties of 1-(4-substituted phenyl)-1-alkyl(aryl)-2-phenyl-3-piperidinopropan-1-ols by N. K. Gasparyan; L. A. Vardevanyan; D. É. Egiazaryan; M. N. Malakyan; S. A. Badzhinyan; D. A. Avakimyan; G. A. Panosyan; G. A. Gevorgyan (224-227).
Interaction of α-phenyl-β-piperidino-4-substituted propiophenones with Grignard reagents in ether was used to synthesize 1-(4-substituted phenyl)-1-alkyl(aryl)-2-phenyl-3-piperidinopropan-1-ols. The antibacterial and antioxidant properties of the aminopropanol hydrochlorides were studied. Some of these compounds (3-(4-ethoxyphenyl)-2-phenyl-1-piperidinoheptan-, 3-(4-ethoxyphenyl)-2-phenyl-1-piperidonooctan-, and 2-phenyl-1-piperidino-3-(4-propoxyphenyl)decan-3-ol hydrochlorides) had moderate antibacterial activity and some (3-(4-ethoxyphenyl)-2-phenyl-1-piperidinopentan- and 3-(4-ethoxyphenyl)-5-methyl-2-phenyl-1-piperidinohexan-3-ol hydrochlorides) had high antioxidant activity.
Keywords: Aminomethylation; β-piperidinopropiophenones; piperidinopropan-1-ols; antibacterial and antioxidant activity

Synthesis and biological activity of substituted 2-iminobenzo[f]coumarin-3-carboxylic acid amides by S. V. Ukhov; B. Ya. Syropyatov; V. V. Novikova; V. A. Balabash; A. S. Shustov; T. F. Odegova (228-230).
Interaction of 2-hydroxynaphthaline-1-carbaldehyde with cyanoacetic acid arylamides was used to synthesize substituted 2-iminobenzo[f]coumarin-3-carboxylic acid amides. Heating of substituted 2-iminobenzo[f]coumarin-3-carboxylic acid amides with acetic anhydride led to the synthesis of acetyl derivatives of this acid. The anticoagulant and antimicrobial activities of these compounds were studied.
Keywords: Amides; 2-iminobenzo[f]coumarin-3-carboxylic acid; synthesis; anticoagulant and antimicrobial activities

Synthesis and antimicrobial activity of 2-aroylmethylene-6-hydroxy-2,3-dihydroindol-3-ones by V. L. Gein; V. V. Tatarinov; N. A. Rassudikhina; M. I. Vakhrin; É. V. Voronina (231-232).
The interaction of methyl esters of aroylpyruvic acids with 2-aminophenol was used to form 2-aroylmethylene-6-hydroxy-2,3-dihydroindol-3-ones. The structures of these compounds were verified by IR and 1H NMR spectroscopy; the antimicrobial activity of the compounds synthesized here was studied.
Keywords: Synthesis; antimicrobial activity; 2-aroylmethylene-6-hydroxy-2,2-dihydroindol-3-ones

Analysis and assay of flavonoid content in the vegetative and reproductive organs of the showy tick trefoil by G. Puodzhyunene; V. Kairite; V. Yanulis; L. Ivanauskas; A. Razhukas; Z. Barsteigene (233-236).
We report here a many-year study of the qualitative and quantitative content of flavonoids in the reproductive organs of the showy tick trefoil (Desmodium canadense (L.) DC., Fabaceae) - stems, leaves, buds, inflorescences,pods, and seeds - collected at different phases of growth at the Department of Medicinal Plants, Kaunas Botanical Garden, Vytautas Magnus University. HPLC studies identified 15 aglycone and glycoside flavonoids: apigenin, apigenin-7-O-glycoside, luteolin, rutin, vicenin-2, vitexin, isovitexin, vitexin rhamnoside, orientin, homoorientin, quercetrin, quercetin, hyperoside, astralagin, and kaempferol. The largest quantities of flavonoids in the vegetative organs from year 2 to year 4 of plant growth were present in the leaves (2.64% and 2.61% at budding and flowering in the second year respectively), while during year 5 maximum quantities were present during budding, flowering, and the beginning of fruiting, during year 6 in budding, and during year 7 during regrowth and budding. In stems, the greatest flavonoid quantities accumulated during the second year of growth during budding and flowering (up to 0.61%). In the reproductive organs, the maximum quantities of flavonoids accumulated in the inflorescences during years 3 – 6 of growth, reaching 2.37% in the flowering phase in year 6. Thus, not only the herb part, but also the leaves of the showy tick trefoil can be used as raw material for herbal remedies. The optimum time for collecting leaves is during flowering, the onset of fruiting, and budding of regrowth after mowing, and the plantation lifetime is seven years.
Keywords: Desmodium canadense ; vegetative organs; herb; reproductive organs; flavonoids; growth phases

Empirical mathematical simulation was used to develop a model for the production of an aqueous extract of birch leaves. This model established that preparation of the aqueous extract required 5 min on a tile or open heat source to obtain a satisfactory yield of flavonoids. The ratio of raw material to water was determined giving the best compromise between the birch leaf extraction efficiency and the therapeutic efficacy of the resulting aqueous extract – this ratio was 1:25. The polarity of birch leaf flavonoids was assessed using the Davies hydrophilic-lipophilic balance and the log coefficient of distribution in a system consisting of octan-1-ol and water.
Keywords: Aqueous birch leaf extract; production model

A new preparative method for the synthesis of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid by V. G. Tribulovich; A. V. Garabadzhiu; I. Kalvin’sh (241-244).
A new method for the synthesis of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (adapalene) was developed, characterized by stable high yields of intermediate and end products, simple scale-up, and technical feasibility.
Keywords: Adapalene; 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid; 3-(1-adamantyl)-4-methoxyphenylboronic acid; synthesis; Suzuki-Miyaura cross-coupling

Formation of ultrathin protective films for ophthalmological use from aqueous solutions of polymers and taurine by S. A. Kedik; S. M. Levachev; A. V. Panov; I. V. Sakaeva; A. E. Kharlov; O. A. Grigor’eva; E. S. Zhavoronok; Yu. V. Cherta; M. A. Zaitsev; Ha Kam An (245-247).
Aqueous dextran solutions, polyhexamethyleneguanidine hydrochloride and Sovidone and their mixtures with taurine were used to form stable ultrathin protective films for ophthalmological use. Addition of taurine to dextran and polyhexamethyleneguanidine solutions induced an association between polymer macromolecules in the two-dimensional film and a decrease in the surface activity of the solution. Addition of taurine to Sovidone solutions altered the conformation of macromolecular globules and increased the surface activity of the solution. Use of these solutions as the bases for eye drops did not harm the lipid layer of the tear film, and that rapidly formed polymer films could successfully be replaced by natural lipids via natural processes during recovery of the functions of the tear glands.
Keywords: Ultrathin protective films; taurine; polymers; eye drops

A simple strategy is described for the domino synthesis of 4-(4-morpholinophenyl)-6-aryl-6H-1,3-thiazin-2-amines (10 – 18) under focused microwave irradiation using NaHSO4 · SiO2 heterogeneous catalyst in dry media. All the synthesized compounds exhibited a broad spectrum of in vitro microbiological activity.
Keywords: domino reaction; 4-(4-morpholinophenyl)-6-aryl-6H-1,3-thiazin-2-amines; thiourea; antibacterial activity; NaHSO4 · SiO2 ; antifungal activity

Assay of amoxicillin in capsules performed in accordance with the US Pharmacopeia by liquid chromatography was compared with a method based on mercurimetric titration, developed by ourselves, in which the internal indicator was an azo derivative of theophylline, i.e., benzenesulfonamide, N-(2,6-dimethoxy-4-pyrimidinyl)- 4-[(4-methylamino-5-methylcarbamoyl)]azo [CA Index Name, i.e., chemical name according to the rules and conventions of the “9th Collective Index of the Chemical Abstracts Service.”]. The analysis results showed that mercurimetric assay was specific and easily performed in laboratory conditions and can be used as an alternative method.
Keywords: Amoxicillin; liquid chromatography; mercurimetry; internal indicator; theophylline azo derivative