In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

Drug Discovery Today

Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance.

The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb.

Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

Tetrazoles via Multicomponent Reactions.

Properties of responsible for biological activity tetrazoles are considered. Examples are given of active pharmaceutical ingredients of modern drugs containing the tetrazole ring in the molecular structure. New publications on the synthesis and investigations of biological activity of promising tetrazole-containing compounds are cited.

Medicinal chemistry of tetrazoles

Respiratory viral infections constitute the most frequent reason for medical consultations in the World. They can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more devastating conditions such as pneumonia. In particular, in serious cases influenza A leads to pneumonia, which is particularly fatal in patients with cardiopulmonary diseases, obesity, young children and the elderly. In the present study, we show a protective effect of the low-molecular weight compound Ingavirin (6-[2-(1H-imidazol-4-yl)ethylamino]-5-oxohexanoic acid) against influenza A (H1N1) virus, human parainfluenza virus and human adenovirus infections in animals. Mortality, weight loss, infectious titer of the virus in tissues and tissue morphology were monitored in the experimental groups of animals. The protective action of Ingavirin was observed as a reduction of infectious titer of the virus in the lung tissue, prolongation of the life of the infected animals, normalization of weight dynamics throughout the course of the disease, lowering of mortality of treated animals compared to a placebo control and normalization of tissue structure. In case of influenza virus infection, the protective activity of Ingavirin was similar to that of the reference compound Tamiflu. Based on the results obtained, Ingavirin should be considered as an important part of anti-viral prophylaxis and therapy.

Activity of Ingavirin (6-[2-(1H-Imidazol-4-yl)ethylamino]-5-oxo-hexanoic Acid) Against Human Respiratory Viruses in in Vivo Experiments

BackgroundInfluenza is a disease of significant morbidity and mortality, the number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. In this work, we demonstrate activity of some usnic acid (UA) derivatives against influenza virus in vitro and in vivo.MethodsOrganic synthesis was used to prepare compounds. Antiviral activity of the compounds in vitro was evaluated by their ability to decrease the virus titer on Madin–Darby Canine Kidney cells. In vivo activity was evaluated by decrease of mortality and index of protection.ResultsCompounds were tested against a broad spectrum of influenza virus strains and showed activity against all used strains. One compound, [5] (valine enamine of UA), also significantly reduced lethality of infected animals and does not give rise to the appearance of resistant strains. Additional studies showed that hepatotoxicity of compound [5] is reduced comparatively to UA.ConclusionOur results suggest that valine enamine of UA could be ...

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Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection

Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity

Synthesis of New Compounds Combining Adamantanamine and Monoterpene Fragments and their Antiviral Activity Against Influenza Virus A(H1N1)pdm09

The purpose of the study was to evaluate the modulating effect of glutamyl-tryptophan (EW), glycyrrhizic acid (GA), and their combination on the course of experimental infection caused by influenza A (H3N2) virus in mice. The animals were infected with influenza A/Aichi/2/68 (H3N2) virus in a dose of 1 or 10 LD50. GA (10 mg/kg body weight) and EW (0.1, 10, and 1000 µg/kg) alone or in combination were intraperitoneally injected for 5 days, starting on day 1 of virus infection. Rimantadine 50 mg/day was used as a comparison drug. The combination of EW (1000 µg/kg) was ascertained to exert the maximum protective effect manifesting itself in reducing the death of infected animals (by 75-79% compared to the control depending on the viral dose) and the titers of viruses accumulated in the lung (5-6 log EID50) and in preventing lung tissue edema and inflammation. The noted effect was comparable with that seen in the use of rimantadine. The agents used alone had a lower efficacy than rimantadine. The finding permit the combination of GA and EW to be considered to be a promising agent for the treatment of influenza.

Anna A. Shtro

Papers

Activity of Ingavirin (6-[2-(1H-Imidazol-4-yl)ethylamino]-5-oxo-hexanoic Acid) Against Human Respiratory Viruses in in Vivo Experiments

Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection

Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity

Synthesis of New Compounds Combining Adamantanamine and Monoterpene Fragments and their Antiviral Activity Against Influenza Virus A(H1N1)pdm09

[Effect of a combination of glutamyl-tryptophan and glycyrrhizic acid on the course of acute infection caused by influenza (H3H2) virus in mice].