Nitronium salts as novel reagents for the heterocyclization of gem-bromofluorocyclopropanes into pyrimidine derivatives

Sedenkova, Kseniya N.; Averina, Elena B.; Grishin, Yuri K.; Bacunov, Aleksandr B.; Troyanov, Sergey I.; Morozov, Igor; Deeva, Evgeniya B.; Merkulova, Anna V.; Kuznetsova, Т. S.; Зефиров, Н. С.

doi:10.1016/j.tetlet.2015.06.089

Cited by 24 publications

(8 citation statements)

References 33 publications

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“…The compounds were synthesized from commercially available starting materials by previously described methods 16 , 23 , 24 and stored as solutions in DMSO at −20°C.…”

Section: Methodsmentioning

confidence: 99%

Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

Dueva

Tuchynskaya

Kozlovskaya

et al. 2020

Antivir Chem Chemother

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Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC50 values lower than 22 µM against all the tested strains. Nevertheless, EC50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.

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“…The compounds were synthesized from commercially available starting materials by previously described methods 16 , 23 , 24 and stored as solutions in DMSO at −20°C.…”

Section: Methodsmentioning

confidence: 99%

Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

Dueva

Tuchynskaya

Kozlovskaya

et al. 2020

Antivir Chem Chemother

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“…A similar synthetic scheme was carried out to obtain compounds 1o , p , containing one and two pyrimidine N -oxide moieties, respectively ( Scheme 3 ). 4-Fluoropyrimidine N -oxide 6 , readily available via heterocyclisation of 7-bromo-7-fluorobicyclo[4.1.0]heptane [ 42 , 43 ], was used as a starting compound. It should be noted that pyrimidine N -oxides 6 , 8 turned out to be less reactive and more labile in the S N Ar reaction conditions, compared with the corresponding pyrimidines, which made us increase the reaction time and caused a decrease in the preparative yields ( Scheme 3 ).…”

Section: Resultsmentioning

confidence: 99%

Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis

et al. 2022

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Positive allosteric modulators (PAMs) of AMPA receptors represent attractive candidates for the development of drugs for the treatment of cognitive and neurodegenerative disorders. Dimeric molecules have been reported to have an especially potent modulating effect, due to the U-shaped form of the AMPA receptor’s allosteric binding-site. In the present work, novel bis(pyrimidines) were studied as AMPA receptor modulators. A convenient and flexible preparative approach to bis(pyrimidines) containing a hydroquinone linker was elaborated, and a series of derivatives with varied substituents was obtained. The compounds were examined in the patch clamp experiments for their influence on the kainate-induced currents, and 10 of them were found to have potentiating properties. The best potency was found for 2-methyl-4-(4-((2-methyl-5,6,7,8-tetrahydroquinazolin-4-yl)oxy)phenoxy)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidine, which potentiated the kainate-induced currents by up to 77% in all tested concentrations (10−12–10−6 M). The results were rationalized via the modeling of modulator complexes with the dimeric ligand binding domain of the GluA2 AMPA receptor, using molecular docking and molecular dynamics simulation. The prediction of ADMET, physicochemical, and PAINS properties of the studied bis(pyrimidines) confirmed that PAMs of this type may act as the potential lead compounds for the development of neuroprotective drugs.

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“…Zefirov and co-workers converted the halogenated cyclopropanes 23 to fluorinated pyrimidine N-oxides (24) under incorporation of a nitrosonium ion and an organic nitrile molecule (Scheme 9a). [32] According to the proposed mechanism, the nitrosonium ion reacts with the strained C-C bond of the cyclopropanes 23. Ring opening gives the positively charged intermediate 23A, which is subsequently scavenged by the nitrile to form 23B.…”

Section: Methodsmentioning

confidence: 99%

Reactive nitrogen species: Nitrosonium ions in organic synthesis

Bering

Antonchick

2019

Tetrahedron

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Nitronium salts as novel reagents for the heterocyclization of gem-bromofluorocyclopropanes into pyrimidine derivatives

Cited by 24 publications

References 33 publications

Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

Spectrum of antiviral activity of 4-aminopyrimidine N-oxides against a broad panel of tick-borne encephalitis virus strains

Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis

Reactive nitrogen species: Nitrosonium ions in organic synthesis

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