On the mechanism of the inhibitory action of 2-amino-4,6-dichloropyrimidine on poliovirus growth

Marcialis, Maria Antonietta; Schivo, M. L.; Atzeni, A.; Garzia, A.; Loddo, B

doi:10.1007/bf01943917

Cited by 10 publications

(4 citation statements)

References 3 publications

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“…The parent 2-amino-4,6dichloropyrimidine (B1) was also tested and no antiviral activity was observed (EC 50 [ 100 lg/mL). It is important to mention that antiviral activities described in the literature for this compound required relatively high concentrations in the range of the 100 lg/mL (Marcialis et al, 1973, 1974, La Colla et al, 1975.…”

Section: Antiviralmentioning

confidence: 99%

“…This work was initially motivated by the finding that 2-amino-4,6-dichloropyrimidine inhibits replication of a broad range of viruses such as members of the Herpes, Picorna, and Pox groups (Marcialis et al, 1973(Marcialis et al, , 1974La Colla et al, 1975). It has been reported that maturation of viral particles was prevented as viral proteins synthesized in the presence of this compound were not assembled into new virions La Colla et al, 1977;Marcialis et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

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5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

et al. 2014

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A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier-Haack-Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6dichloropyrimidine with an IC 50 of 2 lM (higher activity than the most potent reference compound) while the IC 50 s of other derivatives were within the range of 9-36 lM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated.

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Section: Antiviralmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

et al. 2014

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“…2-Amino-4,6-dichoropyrimidine (CAS No. 56-05-3) inhibits replication of a broad range of viruses such as members of the Herpes, Picorna, and Pox groups. , In addition to the recognized broad spectrum of biological activities and pharmacologically utilized properties, 2-amino-4,6-dichloropyrimidines inhibit the immune-stimulated production of nitric oxide. − What’s more, it prevents the growth of poliovirus in amino acid-free medium by impairing the assembly of virus RNA and proteins into complete particles . Owing to their potential biological activity, a number of syntheses have been described. − At present, the purification and separation of 2-amino-4-chloro-6-hydroxpyrimidine and 2-amino-4,6-dichoropyrimidine is the last process in the whole synthesis of 2-amino-4,6-dichoropyrimidine.…”

Section: Introductionmentioning

confidence: 99%

“…56-05-3) inhibits replication of a broad range of viruses such as members of the Herpes, Picorna, and Pox groups. 1,2 In addition to the recognized broad spectrum of biological activities and pharmacologically utilized properties, 2-amino-4,6-dichloropyrimidines inhibit the immune-stimulated production of nitric oxide. 2−6 What's more, it prevents the growth of poliovirus in amino acid-free medium by impairing the assembly of virus RNA and proteins into complete particles.…”

Section: Introductionmentioning

confidence: 99%

Solubility Measurement and Modeling of 2-Amino-4,6-dichoropyrimidine in Ten Pure Solvents and (Ethyl Acetate + Ethanol) Solvent Mixtures

Li¹,

Liu²,

Yin³

et al. 2018

J. Chem. Eng. Data

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The basis of purification and further theoretical studies of 2-amino-4, 6-dichoropyrimidine is the solubility and solution thermodynamics in different solvents. In this paper, the solubility of 2-amino-4,6-dichoropyrimidine in 10 neat solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, toluene, and cyclohexane) and binary liquid mixtures (ethyl acetate + ethanol) was measured by the isothermal saturation method at temperatures range from 278.15 to 318.15 K, at p = 101.2 kPa. High-performance liquid chromatography (HPLC) was used to analyze the solubility of 2-amino-4,6-dichoropyrimidine in selected solvents. To sum up, the equilibrium mole fraction solubility was highest in 1,4-dioxane (2.619 × 10 −2 at 318.15 K) and lowest in cyclohexane (0.02238 × 10 −2 at 318.15 K), and ranked as 1,4-dioxane (2.619 × 10 −2 at 318.15 K) > acetone (1.630 × 10 −2 at 318.15 K) > ethyl acetate (1.471 × 10 −2 at 318.15 K) > acetonitrile (0.5048 × 10 −2 at 318.15 K) > methanol (0.3888 × 10 −2 at 318.15 K) > ethanol (0.3391 × 10 −2 at 318.15 K) > n-propanol (0.3133 × 10 −2 at 318.15 K) > toluene (0.2737 × 10 −2 at 318.15 K) > isopropanol (0.2574 × 10 −2 at 318.15 K) > cyclohexane (0.02238 × 10 −2 at 318.15 K). The achieved solubility values in monosolvents were correlated by the modified Apelblat equation, λh equation, Wilson model, and NRTL model and in solvent mixtures by three cosolvency models including Jouyban-Acree model, van't Hoff-Jouyban-Acree model, and Apelblat-Jouyban-Acree model. Calculated results fitted well with experimental data. Consequently, for the monosolvents, the values of rootmean-square deviation (RMSD) and relative average deviation (RAD) were less than 0.58 × 10 −4 and 0.80%, respectively, and for the binary solvent mixtures were 0.49 × 10 −4 and 0.46%. Furthermore, the Gibbs energy, mixing enthalpy, mixing entropy, activity coefficient at infinitesimal concentration (γ 1 ∞ ) and reduced excess enthalpy (H 1 E,∞ ) in monosolvents, and dissolution property in mixed solvents were computed. The mixing process of 2-amino-4,6-dichoropyrimidine in the studied solvents was spontaneous and endothermic. The obtained solubility and thermodynamic studies would be used to optimize the purification process of 2-amino-4,6-dichoropyrimidine.

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Bichlorinated Pyrimidines as Possible Antiviral Agents

Colla

Marcialis

Flore

et al. 1976

Parasites, Fungi, and Viruses

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On the mechanism of the inhibitory action of 2-amino-4,6-dichloropyrimidine on poliovirus growth

Cited by 10 publications

References 3 publications

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

Solubility Measurement and Modeling of 2-Amino-4,6-dichoropyrimidine in Ten Pure Solvents and (Ethyl Acetate + Ethanol) Solvent Mixtures

Bichlorinated Pyrimidines as Possible Antiviral Agents

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