Novel purine conjugates with N-heterocycles: synthesis and anti-influenza activity

Chemistry of Heterocyclic Compounds - A number of novel amides were synthesized by coupling of 6-[(9H-purin-6-yl)amino]hexanoic acid to heterocyclic amines. The antiviral activity of the obtained...     

Synthesis and antiviral activity of novel imidazo[2,1-b]thiazoles coupled with morpholine and thiomorpholines

Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio-morpholine coupled imidazo[2,1-b]thiazoles. The three-step reaction sequence involving the condensation of 1,3-dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α-bromoacetophenones yielded the desired imidazothiazoles 7(a–l) . Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC₅₀: 1.1 μM, C₅₀: >300 μM, SI = 273) and 7e (IC₅₀: 2.0 μM, C₅₀: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti-influenza hit analogs for further structural optimization.     

Phase Equilibria and Critical Phenomena in the Potassium Nitrate-Water-Diethylamine Ternary System

Phase equilibria and critical phenomena in the potassium nitrate—water—diethylamine ternary system were studied by the visual polythermal method over the temperature range 40–150°C. The corresponding boundary binary liquid system was characterized by stratification with the lower critical temperature of solution. The introduction of potassium nitrate into the water—diethylamine system lowered its lower critical temperature of solution from 146.1 to 48.1°C and decreased the mutual solubility of the components. The diethylamine distribution coefficients between the aqueous and organic monotectic equilibrium phases at various temperatures were calculated. The effect of the salting out of diethylamine from aqueous solutions under the action of potassium nitrate was found to strengthen as the temperature increased. The constructed isotherms of the phase states of the system substantiated the generalized topological scheme of the transformation of phase diagrams of salt-binary solvent ternary systems with salting out.     

Topological transformation of the cesium nitrate-water-isopropanol ternary phase diagram

Phase equilibria and critical phenomena in the cesium nitrate-water-isopropanol system, where the liquid binary subsystem does not separate over the entire temperature range of its liquid state, were studied within 70–120°C using visual polythermal analysis. The temperature at which the monotectic critical tie-line appears (79.0°C) and the compositions of the solutions at critical solution points at various temperatures were determined. Isopropanol distribution coefficients between aqueous and organic monotectic phases were calculated for five temperatures. The salting out of isopropanol by cesium nitrate from aqueous solutions is enhanced by temperature elevation. The phase isotherms validated a previously reported fragment of the general scheme of the topological transformation of ternary phase diagrams for salt-binary solvent systems with salting out. Original Russian Text ? D.G. Cherkasov, V.F. Kurskii, S.I. Sinegubova, K.K. Il’in, 2009, published in Zhurnal Neorganicheskoi Khimii, 2009, Vol. 54, No. 6, pp. 1032–1036.     

Salting-Out of <Emphasis Type="Italic">n</Emphasis>-Propyl Alcohol with Potassium Nitrate from Aqueous Solutions

The solubility of components and critical phenomena in the ternary system constituted by potassium nitrate, water, and n-propyl alcohol were studied by the visual polythermal method in the temperature range 25–80°C. The temperature of formaiton of the critical node of the monotectic equilibrium (critical solution-solid phase) and the solution compositions corresponding to the critical solution points at different temperatures were determined. The isothermal solubility diagrams of the system were constructed and the distribution coefficients of n-propyl alcohol at different temperatures were calculated. A comparative analysis of the salting-out effect exerted by potassium nitrate on aqueous solutions of n-propyl alcohol and isopropyl alcohol was done.__________Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 3, 2005, pp. 398–402.Original Russian Text Copyright © 2005 by Sinegubova, Cherkasov, Il’in.     

Salting-out of isopropyl alcohol from aqueous solutions with potassium nitrate

The solubility of components and critical phenomena in a ternary system constituted by potassium nitrate, water, and isopropyl alcohol were studied by the visual-polythermic method in the temperature range 25–90°C. The formation temperature of the critical node of the monotectic equilibrium (critical solution—solid phase) and the solution compositions corresponding to the critical solubility points at different temperatures were determined. Isothermal solubility diagrams of the system were constructed, the previously suggested scheme of the topological transformation of the phase diagrams of ternary stratifying systems constituted by a salt and a binary solvent was confirmed, and the distribution coefficients of isopropyl alcohol at different temperatures were calculated.Translated from Zhurnal Prikladnoi Khimii, Vol. 77, No. 12, 2004, pp. 1945–1949.Original Russian Text Copyright © 2004 by Sinegubova, Ilin, Cherkasov, Kurskii, Tkachenko.     

Synthesis and antiviral activity of novel 3-substituted pyrazolinium salts

Chemistry of Heterocyclic Compounds - For the first time, convenient methods for the preparation of pyrazoline N-alkylidene salts based on terpene (camphor, camphorquinone, carvone) ketones, cage...     

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC₅₀ = 45.3 µM), Ebola pseudotype viruses (IC₅₀ = 0.12 µM), and authentic EBOV (IC₅₀ = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC₅₀ = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.     

Search for Compounds with Antiviral Activity Among Maleopimaric Acid Derivatives

Chemistry of Natural Compounds - Three new maleopimaric acid derivatives were synthesized. The antiviral activity of 14 synthesized maleopimaric acid derivatives was tested against influenza virus...     

Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity

Molecular Diversity - An effective technique for one-stage synthesis of new polycyclic nitrogen-containing compounds has been developed. The procedure involves refluxing mixtures of camphoric acid...