Pharmaceutical Chemistry Journal (v.45, #9)

Experience in creating new drugs using traditional technologies by R. G. Glushkov; S. D. Yuzhakov (517-521).
Working hypotheses for the creation of new potential drugs including Class III antiarrhythmic (nibentan, niferidyl), antiallergic (theoritin), and antituberculosis (hixozid) agents are formulated and experimental data on the activity of the obtained compounds are presented.
Keywords: potential drugs; Class III antiarrhythmic agents; nibentan; niferidyl; antiallergic agent; theoritin; antituberculosis agent; hixozid; pharmacological (biological) activity

Synthesis and cytotoxic activity of azidonaphthazarins by N. D. Pokhilo; M. I. Kiseleva; V. F. Anufriev (522-525).
Preparative methods have been developed for the synthesis of azidonaphthazarins. It is established that 2-hydroxy- and 2-alkoxy-6,7-dichloronaphthazarins react regiospecifically with sodium azide in MeOH to yield the corresponding 6-azido derivatives. The cytotoxic activity and contraceptive properties of the synthesized azidonaphthazarins have been investigated using the sperm and eggs of the sea urchin Strongylocentrotus intermedius.
Keywords: naphthazarins; 5,8-dihydroxy-1,4-naphthoquinone; cytotoxic activity; Strongylocentrotus intermedius

Syntheses and radioligand activities of dimebon analogs by A. V. Ivashchenko; O. D. Mit’kin; I. M. Okun’; I. V. Kuznetsova (526-531).
Several analogs of the antihistamine drug dimebon have been synthesized with different linkers connecting a picoline fragment to the tetrahydropyridoindole core. Radioligand activity profiles of the obtained compounds have been studied using a broad set of 30 therapeutic targets. Reduction of the linker length is shown to cause substantial shifts in the activity profiles.
Keywords: dimebon; analogs; synthesis; activity; receptors; activity profile; linkers

A series of 2-thiocyanato-(2-methyl)-3-arylpropionamides and products of their heterocyclization, 2-amino-5-benzyl-(5-methyl)thiazol-4-ones, have been synthesized. The synthesized compounds exhibit rather high antibacterial activity with respect to strains of staphylococci, intestinal rods, aerobic bacilli, and yeast fungi. The majority of these compounds show a clearly expressed anti-candidiasis effect.
Keywords: 2-thiocyanato-(2-methyl)-3-arylpropionamides; 2-amino-5-benzyl-(5-methyl)thiazol-4-ones; antibacterial and antifungal activity

Synthesis and antifungal activity of 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo-[1′,5′-1,2]pyrimido[4,5-d]pyridazin-5(6 h)-ones by V. L. Gein; V. V. Mishunin; E. P. Tsyplyakova; O. V. Vinokurova; M. I. Vakhrin (536-538).
A series of 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo[1′,5′-1,2]pyrimido[4,5-d]pyridazin-5(6H)-ones have been obtained by reaction of equivalent amounts of methyl esters of 7-aryl-6-(2-thienyl)-4,7-dihydrotetrazolo[1, 5-a]pyrimidine-5-carboxylic acids and hydrazine hydrate at 180–190°C in the absence of solvents. The structures of the synthesized compounds have been determined based on spectral data (PMR, IR, high-resolution mass spectrometry). The synthesized compounds were tested for antimicrobial activity.
Keywords: 9-aryl-8-(2-thienyl)-4,9-dihydrotetrazolo[1′,5′-1,2]pyrimido[4,5-d]pyridazin-5(6H)-ones; synthesis; antimicrobial activity

Structure–property relationships in series of natural and synthetic inhibitors of catalytic activity of 15-lipoxygenase by V. R. Khairullina; A. Ya. Gerchikov; I. A. Taipov; H. Boegel; F. S. Zarudii (539-546).
Structural signatures characteristic of high-, medium-, and low-efficiency inhibitors of the catalytic activity of 15-lipoxygenase (15-LOG) have been revealed using the SARD-21 (Structure Activity Relationship & Design) computer system. The degree of their influence on the efficiency of the inhibiting activity was estimated. Based on these data, two models are constructed for predicting the interval of LOG-inhibiting activity of various sulfur-, nitrogen-, and oxygen-containing heterocyclic compounds with an 80% prediction accuracy level for the two recognition methods. The revealed structural features can be used to construct highly selective inhibitors of 15-LOG catalytic activity.
Keywords: inhibitor; structure—property relationship; catalytic activity

Antioxidant, analgesic and anti-inflammatory properties of new ninhydrin adduct of embelin by S. Mahendran; S. Badami; S. Ravi; B. S. Thippeswamy; V. P. Veerapur (547-551).
Based on a reaction of ninhydrin with phenols, a new embelin-ninhydrin adduct has been synthesized and characterized. The adduct exhibits high antioxidant activity in the DPPH test. The analgesic and anti-inflammatory activity was also found to be better than that of the parent compound (embelin). In the acetic-acid-induced writhing test, almost complete abolition of writhing was observed at 10 and 20 mg/(kg body weight) doses of embelin-ninhydrin adduct and the results were better than those achieved with the standard drug pentazocine.
Keywords: Embelin, ninhydrin; free radicals, analgesic, carrageenan

Some 17β-acetyl steroids have been converted into 21-hydroxy-20-ketosteroids in high yields upon treatment with phenyliodosodiacetate in methanolic potassium hydroxide. Attempts to carry out the same reaction with several 17α-acetyl steroids derivatives were unsuccessful. The structure of substrates and products was confirmed by the IR, mass spectrometry, and 1H NMR techniques.
Keywords: 21-Monohydroxylation; phenyliodosodiacetate; 17β-acetyl steroids; 17α-acetyl steroids

Separation and identification of components of the multi-component herbal drug prostanorm by V. L. Beloborodov; N. G. Zakharova; A. M. Savvateev; V. K. Kolkhir; I. V. Voskoboinikova (556-559).
Prostanorm is a multi-component Russian herbal drug comprising a mixture of the extracts of St. John’s wort (Hypericum perforatum L.), goldenrod (Solidago canadensis L.), licorice root (Glycyrrhiza glabra L.), and purple coneflower (Echinacea purpurea L. Moench) rhizomes and roots in equal amounts. An HPLC method for qualitative analysis of the components in the mixed phytopreparation and extracts of all individual raw materials has been developed. The optimum chromatographic conditions for HPLC determination of components of the herbal drug have been determined. Components of the mixed extract are satisfactorily separated and resolved by using an octadecylsilane adsorbent and gradient elution with a mixture of acetonitrile, methanol, phosphate buffer, and dimethylformamide. HPLC analysis was optimized according to chromatographic parameters. The basic biologically active components of the herbal mixture and individual extracts of all herbs were identified. The proposed method ensures determination of the identity of the herbal drug Prostanorm in the form of liquid extract for peroral administration.
Keywords: Prostanorm phytopreparation; HPLC; determination of drug components; identity; qualitative analysis

Quantitative HPLC determination of cynaropicrin in Centaurea Scabiosa dry extract by I. P. Kaminskii; E. A. Krasnov; T. V. Kadyrova; S. A. Ivasenko; B. B. Rakhimova; S. M. Adekenov (560-563).
An HPLC method for quantitative determination of cynaropicrin in Centaurea scabiosa L. dry extract obtained using 40% aqueous ethanol has been developed and its performance has been validated. The proposed method is specific; ensures high accuracy, reproducibility, and linearity in an analytical range of ±30%; and can be used for reliable quality control of C. scabiosa L. dry extract and related preparations.
Keywords: Centaurea scabiosa ; cynaropicrin; quantitative determination; HPLC; validation

Development of synthesis technology for the selective anxiolytic drug afobazole by N. I. Avdyunina; B. M. Pyatin; L. N. Grushevskaya; T. Ya. Mozhaeva; R. F. Bol’shakova; M. I. Ustinova (564-567).
The optimum synthetic scheme, methods of obtaining intermediates, and stage-by-stage analytical control techniques have been developed for industrial manufacturing of the new anxiolytic drug afobazole. According to the scheme, 2-nitro-p-phenethidine reduction by sodium dithionite is followed by cyclization of the diamine with potassium ethylxanthate. Alkylation of 2-mercapto-5-ethoxybenzimidazole with 4-(2-chloroethyl) morpholine was carried out. Thus, the technology for obtaining afobazole parent substance of pharmacopoeial quality is worked out.
Keywords: afobazole parent substance; phenacetin; nitration; sodium dithionite; reduction; cyclization; 2-mercapto-5-ethoxybenzimidazole; chloroethylmorpholine hydrochloride; 2-[2-(morpholino)ethylthio]-5-ethoxybenzimidazole dihydrochloride

Synthesis and characterization of a new carrier based on Eudragit® EPO/S100 interpolyelectrolyte complex for controlled colon-specific drug delivery by R. I. Mustafin; A. V. Bukhovets; A. Yu. Sitenkov; V. R. Garipova; V. A. Kemenova; P. Rombaut; G. Van den Mooter (568-574).
With a view to the development of peroral controlled drug delivery systems, a new interpolyelectrolyte complex (IPEC) between oppositely charged types of Eudragit®, EPO and S100, has been synthesized and investigated at neutral pH values. According to data of turbidimetry, capillary viscometry, gravimetry, and elemental analysis, the obtained IPEC has a composition of Z = [EPO]/[S100] = 1.26. Structural features of the IPEC samples have been evaluated by FTIR spectroscopy and modulated-temperature differential scanning calorimetry. The results confirmed that the IPEC is stabilized by cooperative intermacromolecular ionic bonds, is chemically homogeneous, and is characterized by a single glass transition temperature. The observed features of the carrier swelling and diclofenac sodium release from the matrix system confirm that the proposed IPEC has great potential to be used as a carrier for controlled colon-specific drug delivery.
Keywords: synthesis; interpolyelectrolyte complex; Eudragit® EPO and S100; matrix system; colon-specific controlled drug delivery

Development of composition and technology for immunstifin capsules by M. M. Rakhmatullaeva; S. N. Aminov (575-578).
The physicochemical and technological properties of immunstifin parent substance (salidroside obtained from the dry extract of Rhodiola rosea) have been studied in order to select the composition and optimize the technology of the drug in capsules. The results showed the necessity of introducing excipients into the capsule composition. The best characteristics were obtained with the addition of starch, aerosil, and magnesium stearate in the following amounts: immunstifin substance, 0.1 g; potato starch, 0.098; aerosil, 0.0002; magnesium stearate, 0.0018. The average mass of a capsule is about 0.2000 g. This mixture was used to fill capsules soluble in the acidic media of gastric juice. Tests with immunstifin capsules in 0.1% solution met the pharmacopoeial quality requirements with respect to disintegration, dissolution, appearance, and all other indices.
Keywords: immunstifin; salidroside; aerosil; capsules; calcium stearate; magnesium stearate; starch; dry extract

Obituary (579-579).