Pharmaceutical Chemistry Journal 

About: Pharmaceutical Chemistry Journal is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Chemistry & Antimicrobial. It has an ISSN identifier of 0091-150X. Over the lifetime, 9865 publications have been published receiving 24769 citations.

Benzimidazole derivatives: Spectrum of pharmacological activity and toxicological properties (a review)

Abstract: The properties of benzimidazole and its derivatives have been studied over more than one hundred years [1]. However, a special interest of researchers toward this class of compounds was stimulated by the fact that 5,6-dimethylbenzimidazole is a component of vitamin Bi2 [2]. Shortly after, it was established that, albeit vitamin B~2 is capable of stimulating the growth of bacteria, the benzimidazole fragment and some of its derivatives suppress the bacterial growth. This discovery was followed by attempts to create new antibacterial preparations based on the benzimidazole derivatives. Antibacterial and antiviral activity. A series of halogen-substituted 5,6-dimethylbenzimidazole derivatives exhibit pronounced antibacterial and antiviral properties [3 7]. This is explained by their competition with purines resulting in inhibition of the synthesis of microbial nucleic acids and proteins [3, 6 8]. Derivatives of pyrimido[ 1,6-a]benzimidazole represent a new class of DNA-gyrase inhibitors, which are effective antibacterial agents [9]. Antimicrobial and antifungal properties were reported for 3-alkylthiomethyl-l-ethyl-, 3-alkoxymethyl-l-butyl-, and 3-alkylthiomethyl-l-butylbenzimidazolium chlorides, as well as for 2-chloromethyl-5Hmethylbenzimidazoles [10, 1 l]. Some 5-nitrobenzimidazole derivatives also exhibit fungicidal activity [12]. Certain antimicrobial and antifungal potential was observed in heterocyclic benzimidazole derivatives [13]. It was established that 1-(2,6-difluorophenyl)-lH,3Hthiazolo[3,4-a]benzimidazole (triazobenzimidazole) produces an antiviral effect by inhibiting the non-nuclear reverse transcriptase activity [14]. This preparation has proved to be effective against the H1V-1 infection, the effect resulting from selective inhibition of the reverse transcriptase of HIV1 (but not HIV-2). Sulfoxide and sulfonic metabolites of thia-

Validation of HPLC Techniques for Pharmaceutical Analysis

Abstract: Validation (evaluation of suitability) of an analytical technique is a procedure aimed at obtaining experimentally justified evidence of the ability of this technique to give results characterized by the required accuracy and precision [1 – 7]. All analytical techniques used for the development of pharmaceuticals and for the determination of their quality characteristics have to be validated. In the case of using methods stipulated and described in the State Pharmacopoeia, it is not necessary to evaluate their suitability, provided that the analyses are conducted with strict observation of the text of each particular article. In most other cases, especially in cases of modification of the drug composition, the scheme of synthesis, or the analytical procedure, it is necessary to re-evaluate the suitability of the analytical techniques. This paper is aimed at (i) considering the peculiarities of validation of HPLC techniques for pharmaceutical analysis, (ii) critically assessing the main approaches to evaluation of the validation characteristics, and (iii) providing practical recommendations and criteria for finding correct solutions. The USSR State Pharmacopoeia (valid in the Russian Federation) introduced the section “Statistical Analysis of Biological Test Results” in 1968 (Xth Ed.) and the section “ Statistical Processing of Chemical Experimental Data” in 1988 (XIth Ed.). These sections are devoted to problems involved in the metrological attestation of analytical techniques. In 1987, the United States Food and Drug Administration (FDA) issued practical guides on the main principles of validation [5] and on the presentation of samples and analytical data pertaining to the validation of methods [6]. In 1993, the International Conference on Harmonization (ICH) developed generalized recommendations on the validation of analytical procedures; these documents were published in 1994 and treated in more detail in 1995 [1 – 3]. In 1994, the US FDA Center for Drug Evaluation and Research (CDER) issued a guide on the validation of chromatographic methods [4]. These documents and some review papers and monographs [9 – 13] provided a basis for extensive implementation of the procedure of validation of analytical methods. The Internet offers the Laboratory Guide to Method Validation and Related Topics at http://www.eurachem.ul.pt /. In recent years, new guides have become available from CDER [15], Waters Company [16], and Labcompliance [17 – 19]. Special sections are devoted to these problems in national and international pharmacopoeias and guides on the validation of analytical procedures [7, 20 – 22]. Also available are computer program packages, such as ELISA Method Validation Templates (Waters) and LaChrom 2000 Validation Manager (Merck) representing electronic tables with incorporated functions of statistical processing of the results of measurements and issuing validation certificates, and monographs on the related subjects [23 – 34]. Tables 1 and 2 summarize the most recent recommendations concerning selection of the validation characteristics depending on the type of analytical procedures. A comparative analysis of these data shows that, according to the United States Pharmacopoeia (USP-26), methods of dissolution testing have to be validated only with respect to precision (repeatability, reproducibility), while the other characteristics “may require validation, depending on the specific test nature.” In contrast, according to the FDA CDER guidelines [15], procedures used for quantitative analysis and dissolution testing need the same validation characteristics. Pharmaceutical Chemistry Journal Vol. 38, No. 4, 2004

Adamantane derivatives: Pharmacological and toxicological properties (review)

Abstract: Original papers describing the biological properties of adamantane-containing drugs reported on the antiviral activity of 1-aminoadamantane [1]. Presently, the amino derivatives of adamantane are widely used for the prophylaxis and treatment of various viral diseases [2 -4 ] and parkinsonism [5 7]. Six adamantane derivatives are currently used in modem medicine, and two novel preparations have been recently certified.

Synthesis and antiviral activity of fluorinated pyrido[1,2-a]benzimidazoles

Abstract: Methods for the synthesis of fluorinated pyrido[1,2-a]benzimidazoles have been developed, and a series of such compounds has been obtained and studied for biological activity. In particular, 5,6-difluoro-2-cyanobenzimidazole (II) was synthesized for the first time using the reaction of 1,2-diamino-4,5-difluorobenzole (I) with cyanoacetic ether. Pyrido[1,2-a]benzimidazoles (III, IV) were obtained via condensation of benzimidazole II with diethylethoxymethylene malonate and ethyl acetoacetate. The synthesized pyrido[1,2-a]benzimidazoles (III–XIII) were subjected to screening on a culture of Vero cells for antiviral activity and cytotoxicity with respect to ortho-poxviruses that are pathogenic for humans.