Pharmaceutical Chemistry Journal (v.44, #8)

Reaction of 4-amino-3-ethoxycarbonyl-1,2-dihydrospiro(naphthalene-2,1'-cyclohexane) with allylisothiocyanate was used to synthesize 3-allyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline5,1'-cyclohexane). Condensation of the latter with halides of various structure led to a series of 2-sulfanylsubstituted benzo[h]quinazolines. The antimonoaminooxidase and antineoplastic properties of the synthesized compounds were studied.
Keywords: 3-allyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrospiro(benzo[h]quinazoline-5,1'-cyclohexanes); synthesis and antineoplastic and antimonoamineoxidase activity

Synthesis, antineoplastic and antimonoamineoxidase activity of new spiro-derivatives of benzo[h]quinazolines by A. I. Markosyan; S. A. Gabrielyan; F. G. Arsenyan; R. S. Sukasyan; I. S. Sarkisyan (409-412).
The condensation of 4-amino-3-cyano-1,2-dihydrospiro(naphthalene-2,1'-cyclopentane) with y-chlorobutyryl chloride and aromatic acid chlorides yielded amides that were cyclized into 2-substituted 4-oxo3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopentanes). Replacement of the chlorides by nucleophilic reagents (alkoxides, secondary amines, thiolates) was studied. It was established that 2-(y-chloropropyl)-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopropane) underwent intramolecular cyclization to form 6-oxo-2,3,4,5,7,8-hexahydrospiro(benzo[h]pyrrolo[2,1-b]quinazoline-7,1'-cyclopentane) whereas 2-chloromethyl-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1'-cyclopentane) formed substitution products. The antimonoamineoxidase and antineoplastic properties of the synthesized compounds were studied.
Keywords: spiro derivatives of benzo[h]quinazolines; synthesis; antineoplastic and antimonoamineoxidase activity

Synthesis and biological activity of substituted 6-alkyl(6H)-3-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines by M. A. Iradyan; N. S. Iradyan; R. V. Paronikyan; G. M. Stepanyan (413-417).
A series of substituted 6-alkyl(6H)-3-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines have been synthesized by reaction of 3-alkyl-4-amino-5-thio-1,2,4-triazoles with substituted phenacylbromides in the presence of an equimolar amount of KOH. Mass spectra for the dissociative ionization by electron impact, antibacterial activity, and antitumor properties of the synthesized compounds have been studied. It was established that some compounds at doses of 50 – 100 mg/kg decrease the growth of sarcomas 45 and 37 by 35 – 47%.
Keywords: Phenacylbromides; 4-amino-5-thio-1,2,4-triazoles; triazolothiadiazines; dissociative ionization by electron impact; antibacterial activity; antitumor properties

Immunotropic activity of new water-soluble sulfur-containing phenolic compounds by O. P. Kolesnikova; E. A. Krasnov; S. Yu. Klepikova; N. V. Kandalintseva; A. E. Prosenko (418-420).
The immunotropic activity of new water-soluble sulfur-containing phenolic compounds containing di-tert-butyl and dimethylalkyl ortho-substituents has been studied in vitro and on an experimental model of autoimmune pathology in mice. It is established that the compounds inhibit spontaneous and mitogen-stimulated proliferative activity of immunocompetent intact murine splenocytes in vitro. The compounds also exhibit anti-inflammatory and radioprotective activity on models in vivo.
Keywords: phenolic antioxidants; immuntropic preparations

Antioxidant and antiradical properties of new amino-acid derivatives of aminoalcohols by M. G. Malakyan; L. A. Vardevanyan; D. E. Yeghiazaryan; S. A. Badzhinyan; A. G. Agababyan; G. A. Gevorgyan (421-423).
The antioxidant, antiradical, and membranotropic properties of newly synthesized compounds of the group of N-[3-hydroxy-3-(p-substituted phenyl)-1-propyl] amino acids were studied on model systems in vitro.According to the results, amino-acid derivatives of aminopropanols did not exhibit any significant antioxidant or antiradical activity as evidenced by Fe(II)-stimulated ascorbate-dependent peroxidation, by spectrophotometric monitoring of a decrease in the concentration of stable 2,2-diphenyl-1-picrylhydrazyl radical, or by photochemiluminescence techniques. However, these compounds revealed a membrane-stabilizing effect preventing hemolytic destruction of cells under conditions of H2O2-stimulated oxidative stress of erythrocytes. In this respect, derivatives of glycine, leucine, and methionine were most interesting.
Keywords: aminopropanols; amino acids; antioxidant properties; antiradical activity; erythrocytes; oxidative stress; hemolysis; membranotropic properties

A series of cyclopentylhalogenoanisoles have been synthesized by alkylation of o- and p-chloro- and fluoroanisoles with cyclopentene in the presence of BF3·H3PO4. The compositions and structures of the products were studied by GC, IR, and NMR spectroscopy. Demethylation of the cyclopentylhalogenoanisoles yielded cyclopentylhalogenophenols, which were reacted with chloroacetic acid and chloroacetamide to obtain cyclopentyl-substituted chloro- and fluorophenoxyacetic acids and their amides. Results of studying the antimicrobial activity of the synthesized acids and their amides against S. viridans, S. flexneri, P.aeruginosa, B. antracoides, K. rhinoscleromatis, and C. albicans are presented. All substances show moderate activity against the test microbes (minimum bacteriostatic concentrations from 31.25 to 125 μg/mL). Introduction of a cyclopentyl substituent into the structure of 2-chlorophenoxyacetic acid improves the activity against S. viridans, P. aeruginosa, and K. rhinoscleromatis. These data can be used to study the relationship between the structures and antimicrobial activity.
Keywords: cyclopentene; cyclopentyl-substituted chloro- and fluorophenoxyacetic acids and their amides; antimicrobial activity

Synthesis and antimicrobial activity of dialkyl-2-aryl-6-hydroxy-6-methyl-4-( p-toluenesulfonylaminoimino) cyclohexane-1,3-dicarboxylates by V. L. Gein; A. S. Prusakova; N. V. Nosova; M. I. Vakhrin; E. V. Voronina; A. P. Kriven’ko (427-429).
Reaction of dialkyl-2-aryl-6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxylates with tosylhydrazide proceeds via the alicyclic carbonyl group to give dialkyl-2-aryl-6-hydroxy-6-methyl-4-(p-toluenesulfonylaminoimino) cyclohexane-1,3-dicarboxylates. The antimicrobial activity of the synthesized compounds has been evaluated.
Keywords: synthesis; antimicrobial activity; dialkyl-2-aryl-6-hydroxy-6-methyl-4-(p-toluenesulfonylaminoimino) cyclohexane-1,3-dicarboxylates

Synthesis and antimicrobial activity of 2-alkyl-1-[2′-chloro(diethylamino, morpholino)methylcarbonylethoxy]pyrroles by R. A. Hajili; R. F. Gakhramanov; A. A. Mamedova; Z. O. Karaev; S. K. Zeinalova; R. I. Ibragimov; Sh. F. Nagieva; T. S. Mekhtieva (430-432).
A series of previously unreported 2-alkyl-1-(2-chloromethylcarbonylethoxy)pyrroles have been synthesized via reaction of 2-alkly-1-(2-hydroxyethyl)pyrroles with chloroacetyl chloride and reaction of the intermediates with secondary amines to give 2-alkyl-1-[2-diethylamino(morpholino)methylcarbonylethoxy]pyrroles. Their antimicrobial activity has been studied. It is established that electron-accepting substituents in the methylcarbonylethoxy chain increase whereas electron-donating ones decrease the antimicrobial activity of the pyrroles in the order chlorine > morpholine > diethylamine.
Keywords: 1-(2-hydroxyethyl)pyrroles; 1-[2-chloro(diethylamino)methylcarbonylethoxy]pyrroles; antimicrobial activity; synthesis

Synthesis and antimicrobial activity of new hetrocycles obtained using cyanoacetylation by Sh. M. Abu-Bakr; M. F. El-Shehry; E. M. El-Telbani; G. A. M. Nawwar (433-437).
A straightforward synthesis of various nitrogenated heterocycles using a cyanoacetylating reagent from cyanoacetic acid and acetic anhydride is described. Biological testing of the synthesized compounds for their antibacterial and antifungal activities has been carried out.
Keywords: cyanoacetylation; thiadiazole; imidazolone; antibacterial and antifungal activities

Some novel derivatives of quinazolinone including 2-[2-(2, 6-dichlorophenyl)amino]phenylmethyl-3-{4-[2-(substituted phenyl)-4-oxo-thiazolidin-3-yl]phenylsulfonamido-1-yl}-6-bromoquinazolin-4(3H)ones (4a – 4l) were prepared from 2-[2-(2, 6-dichlorophenyl) amino]phenylmethyl-3-{[4-(N-substituted arylidene)phenyl]-sulfonamide-1-yl}-6-bromo quinazolin-4(3H)ones (3a – 3l). Twenty four synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Minimum inhibitory concentration (MIC) values of all the twenty four compounds were determined. Some of these compounds exhibited significant antimicrobial activity.

Palladium catalysts in the synthesis of local anesthetics (review) by M. V. Klyuev; M. G. Abdullaev; Z. Sh. Abdullaeva (446-451).
Catalytic processes involving Pd-containing catalysts for the synthesis of local anesthetics such as anesthesin (benzocaine), novocaine (procaine), lidocaine, mepivacaine, bupivacaine, trimecaine, and pyromecaine (bumecaine) are reviewed.
Keywords: local anesthetics; synthesis; Pd-containing anion-exchangers; hydrogenation; hydroamination; hydroacylation

New pharmacological preparations based on perfluorocarbon nanoemulsions by S. I. Vorob’ev; A. A. Elapov; A. R. Armasov (452-455).
The technology and some physicochemical and biomedical characteristics of perfluorocarbon (PFC) nanoemulsions are considered. These nanosystems can act as universal nanocarriers under certain technological conditions for preparing biologically active emulsions based on PFC. These emulsions contain nanoparticles that can absorb, penetrate, and affect any systems of an organism and parts of organs and carry on their surface various substances such as gases, organic compounds, solid particles, markers, pharmaceuticals, and active substances. PFC emulsions can perform as blood-plasma-substituting solutions with gas-transport function.
Keywords: perfluorocarbon nanoemulsions; nanosystems; homogenization; obtaining emulsions by dispersion.

Improved synthesis of 2,7-dihydroxyfluorenone in the manufacture of tilorone with application of a rotor—stator system by Yu. A. Kryukov; M. S. Vasilishin; O. S. Ivanov; A. G. Karpov; I. A. Surmacheva; I. R. Akhmadeev; S. V. Sysolyatin (456-458).
A method for improving the quality and increasing the yield of 2,7-dihydroxyfluorenone by using a rotor– stator apparatus in the process technology is described. The results can be used in the manufacturing of tilorone.
Keywords: tilorone; rotor—stator apparatus; 2,7-dihydroxyfluorenone.

Chemical and biological investigation of hydrolysate based on lactic-acid bacterial cultures by G. S. Garanyan; R. A. Khanferyan; E. T. Oganesyan (459-462).
The amino-acid and elemental composition of a hydrolysate based on lactic-acid bacterial cultures has been studied. The quantitative content of amino acids in the hydrolysate is determined and the analytical method is validated with respect to linearity, reproducibility, and accuracy. Investigation of the biological activity of the hydrolysate by three-day cultivation with cells showed evidence for stimulation of the expression of T-lymphocytes (CD3+) and their subpopulation with helper activity (CD4+).
Keywords: amino acids; hydrolysate; immunomodulants; validation; immunomodulating drugs

A new automated method for the quantitative determination of ascorbic acid in the substance, injection forms, and tablets has been developed and validated. The proposed method is based on two versions of capillary electrophoresis: (i) capillary zone electrophoresis and (ii) micellar electrokinetic chromatography. The method shows high accuracy, repeatability, and precision (with both within-run and between-run variation coefficients lower than 1%). The method measures ascorbic acid in a linear manner (r = 0.999) with a detection limit of 8.8 mg/L. The quantity of ascorbic acid in injections amounted to 49.99 ± 0.24 mg/mL; in tablets, 49.39 ± 0.15 mg.
Keywords: ascorbic acid; capillary zone electrophoresis; micellar electrokinetic chromatography; validation

Chemical and pharmaceutical analysis of the new biologically active natural powder klimont by A. N. Zhuchkov; M. S. Goizman; A. S. Berlyand; G. B. Tikhomirova (466-468).
Methods for the standardization of klimont, a new natural biological mixture of minerals, have been developed. They ensure reliable quality control of this pharmaceutical preparation.
Keywords: klimont; quality control indicators; justification and norms of indicators; methods of determination