Category: pyrimidines

Kaczanowska, Katarzyna published the artcileSubstituted 2-Aminopyrimidines Selective for α7-Nicotinic Acetylcholine Receptor Activation and Association with Acetylcholine Binding Proteins, Name: 2-Amino-4,6-dichloropyrimidine, the publication is Journal of the American Chemical Society (2017), 139(10), 3676-3684, database is CAplus and MEDLINE.

Through studies with ligand binding to the acetylcholine binding protein (AChBP), the authors previously identified a series of 4,6 substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, the authors employed HEK cells transfected with cDNA’s encoding three requisite receptor subtypes: α7-nAChR, α4β2-nAChR and a serotonin receptor (5-HT3AR), along with a fluorescent reporter. Initial screening of a series of over 50 newly characterized 2-aminopyrimidines with affinity for AChBP showed only two to be agonists on the α7-nAChR below 10 μM concentration Their unique structural features were incorporated into design of a second subset of 2-aminopyrimidines yielding several congeners that elicited α7 activation with EC₅₀‘s of 70 nM and Kd’s for AChBP in a similar range. Several compounds within this series exhibit specificity for the α7-nAChR, showing no activation or antagonism of α4β2-nAChR or 5-HT3AR at concentrations up to 10 μM, while others were weaker antagonists (or partial agonists) on these receptors. Anal. following cocrystn. of four ligand complexes with AChBP show binding at the subunit interface, but with an orientation or binding pose that differs from classical nicotinic agonists and antagonists and from the previously analyzed set of 2-aminopyrimidines that displayed distinct cooperative interactions with AChBP. Orientations of aromatic side chains of these complexes are distinctive, suggesting new modes of binding at the agonist-antagonist site and perhaps an allosteric action for heteromeric nAChRs.

Journal of the American Chemical Society published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Name: 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

D’Attoma, Joseph published the artcileEfficient Transposition of the Sandmeyer Reaction from Batch to Continuous Process, Computed Properties of 56-05-3, the publication is Organic Process Research & Development (2017), 21(1), 44-51, database is CAplus.

The transposition of Sandmeyer chlorination from a batch to a safe continuous flow process was investigated. Our initial approach was to develop a cascade method using flow chem. which involved the generation of diazonium salt and its quenching with copper chloride. To achieve this safe diazotation continuous process, a chemometric approach (Simplex method) was used and extrapolated to establish a fully continuous flow method. The reaction scope was also examined via the synthesis of several (het)aryl chlorines. Validation and scale-up of the process were also performed. A higher productivity was obtained under increasingly tight security.

Organic Process Research & Development published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Computed Properties of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Ke, Shaoyong published the artcileSubstituted-nicotinyl thiourea derivatives bearing pyrimidine moiety: synthesis and biological evaluation, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is Research on Chemical Intermediates (2011), 37(6), 627-633, database is CAplus.

Several substituted nicotinyl thiourea derivatives containing a pyrimidine ring were designed and the synthesis of the target compounds was achieved in good to excellent yield using PEG-400 as solid-liquid phase transfer catalyst under ultrasound irradiation conditions. The structures of the new compounds were confirmed by IR, ¹H-NMR and elemental anal. The preliminary biol. tests show that some of the target compounds present good inhibitory activities against the root and stalk of Magnoliopsida (dicotyledon plants) and are safe for Liliopsida (monocotyledon plants).

Research on Chemical Intermediates published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Safety of 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Wang, Binju published the artcileComputations Reveal a Rich Mechanistic Variation of Demethylation of N-Methylated DNA/RNA Nucleotides by FTO, HPLC of Formula: 608-34-4, the publication is ACS Catalysis (2015), 5(12), 7077-7090, database is CAplus.

The fat-mass and obesity-associated (FTO) protein employs an iron(IV) oxo species to demethylate N-methylated nucleic acids. Herein, we use atomistic-theor. calculations to study the demethylation of the N-methylated DNA/RNA bases 6-methylated adenine (m⁶A), 3-methylated thymine (m³T), and 3-methylated uracil (m³U). The mechanisms involve in-enzyme hydroxylation of the Me group, followed by hydrolysis of the oxidized intermediates in aqueous solution to demethylate the bases. The in-enzyme reactions have been studied using quantum mech./mol. mech. (QM/MM) calculations, while the hydrolytic reactions occurring outside the enzyme have been explored with hybrid cluster-continuum (HCC) calculations When the results obtained with these different methods are combined, the calculated barrier for the overall transformation is consistent with the exptl. free energy barrier for the major route of m⁶A demethylation: in this pathway, adenine’s N1 site acts as an internal base catalyst in the rate-determining hydrolysis of the hydroxylated hemiaminal intermediate hm⁶A to a demethylated A and formaldehyde. This N1-catalyzed mechanism makes m⁶A the most reactive substrate in comparison to other bases we tested. In the minor, slower, route, two oxidation steps by FTO generate an amide intermediate (f⁶A) that undergoes in-water hydrolysis, producing A and formic acid, as found exptl. In contrast, since m³T and m³U lack internal basic catalytic sites, their hemiaminals decompose with high barriers. The mechanism instead involves two sequential oxidations, leading to demethylated bases and formic acid. Thus, our results, obtained using a holistic approach combining modeling the enzyme and the surrounding aqueous solution, suggest revisions of the exptl. mechanisms for m³T and m³U demethylation.

ACS Catalysis published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C50H65O4P, HPLC of Formula: 608-34-4.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Myrianthopoulos, Vassilios published the artcileTandem virtual screening targeting the SRA domain of UHRF1 identifies a novel chemical tool modulating DNA methylation, Name: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is European Journal of Medicinal Chemistry (2016), 390-396, database is CAplus and MEDLINE.

Ubiquitin-like protein UHRF1 that contains PHD and RING finger domain 1 is a key epigenetic protein enabling maintenance of the DNA methylation status through replication. A tandem virtual screening approach was implemented for identifying small mols. able to bind the 5-methylcytosine pocket of UHRF1 and inhibit its functionality. The NCI/DTP small mols. Repository was screened in silico by a combined protocol implementing structure-based and ligand-based methodologies. Consensus ranking was utilized to select a set of 27 top-ranked compounds that were subsequently evaluated exptl. in a stepwise manner for their ability to demethylate DNA in cellulo using PCR-MS and HPLC-MS/MS. The most active mols. were further assessed in a cell-based setting by the Proximity Ligation In Situ Assay and the ApoTome technol. Both evaluations confirmed that the DNMT1/UHRF1 interactions were significantly reduced after 4 h of incubation of U251 glioma cells with the most potent compound NSC232003, showing a 50% interaction inhibition at 15 μM as well as induction of global DNA cytosine demethylation as measured by ELISA. This is the first report of a chem. tool that targets UHRF1 and modulates DNA methylation in a cell context by potentially disrupting DNMT1/UHRF1 interactions. Compound NSC232003, a uracil derivative freely available by the NCI/DTP Repository, provides a versatile lead for developing highly potent and cell-permeable UHRF1 inhibitors that will enable dissection of DNA methylation inheritance.

European Journal of Medicinal Chemistry published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Name: 2-(Dimethylamino)pyrimidine-4,6-diol.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Segado, Mireia published the artcileUnderstanding the differences in photochemical properties of substituted aminopyrimidines, Product Details of C6H9N3, the publication is Theoretical Chemistry Accounts (2011), 128(4-6), 713-725, database is CAplus.

The luminescent patterns of several members of the aminopyrimidine family are very different, showing not fluorescence at all, only a fluorescence band, normal or anomalous, or dual fluorescence, depending on the substituents and on the environment (gas phase vs. polar solvents). The authors study the lowest excited states of several members of this family that exhibit different fluorescence patterns to try to explain their photochem. and to understand the effect of the substituents and the environment. Several excited states (local excited (LE), charge transfer (CT) and n _N-π^* states) have min. on the lowest excited potential energy surface (S₁), being their relative energy the determinant factor of the luminescent behavior. If the more stable S₁ min. are of n _N-π^* character, a nonradiative deexcitation channel is the most efficient and the system shows no fluorescence. If the CT and/or LE states are the most stable, the nonradiative deactivation channel is not accessible and the system fluoresces. The relative energies of the CT and LE min. (affected by substituents and by the presence of a polar solvent) and the different magnitude of the oscillator strength for the radiative transition to the ground state determine which emission is more efficient, giving place to normal, anomalous or dual fluorescence. The study was carried out by CASSCF/CASPT2 computations, including the solvent effect by the PCM model.

Theoretical Chemistry Accounts published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C9H21NO3, Product Details of C6H9N3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Tessier, Romain published the artcile“Doubly Orthogonal” Labeling of Peptides and Proteins, Formula: C4H3Cl2N3, the publication is Chem (2019), 5(8), 2243-2263, database is CAplus.

Herein, we report a cysteine bioconjugation methodol. for the introduction of hypervalent iodine compounds onto biomols. Ethynylbenziodoxolones (EBXs) engage thiols in small organic mols. and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiol. conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodol. on relevant and complex biomols., such as histone proteins. Through single-mol. experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization.

Chem published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C10H2F12NiO4, Formula: C4H3Cl2N3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Tessier, Romain published the artcile“Doubly Orthogonal” Labeling of Peptides and Proteins, Quality Control of 5738-14-7, the publication is Chem (2019), 5(8), 2243-2263, database is CAplus.

Herein, we report a cysteine bioconjugation methodol. for the introduction of hypervalent iodine compounds onto biomols. Ethynylbenziodoxolones (EBXs) engage thiols in small organic mols. and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiol. conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodol. on relevant and complex biomols., such as histone proteins. Through single-mol. experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization.

Chem published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C3H6O2, Quality Control of 5738-14-7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Fang, Ge-min published the artcileA bright FIT-PNA hybridization probe for the hybridization state specific analysis of a CU RNA edit via FRET in a binary system, Application of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Chemical Science (2018), 9(21), 4794-4800, database is CAplus and MEDLINE.

Given the length required for uniqueness of the targeted segment, the commonly used probes do not provide the level of sequence specificity needed to discriminate single base mismatched hybridization. Herein we introduce a binary probe system based on fluorescence resonance energy transfer (FRET) that distinguishes three possible states i.e. (i) absence of target, (ii) presence of edited (matched) and (iii) unedited (single base mismatched) target. To address the shortcomings of read-out via FRET, we designed donor probes that avoid bleed through into the acceptor channel and nevertheless provide a high intensity of FRET signaling. We show the combined use of thiazole orange (TO) and an oxazolopyridine analog (JO), linked as base surrogates in modified PNA FIT-probes that serve as FRET donor for a second, near-IR (NIR)-labeled strand. In absence of target, donor emission is low and FRET cannot occur in lieu of the lacking co-alignment of probes. Hybridization of the TO/JO-PNA FIT-probe with the (unedited RNA) target leads to high brightness of emission at 540 nm. Co-alignment of the NIR-acceptor strand ensues from recognition of edited RNA inducing emission at 690 nm. We show imaging of mRNA in fixed and live cells and discuss the homogeneous detection and intracellular imaging of a single nucleotide mRNA edit used by nature to post-transcriptionally modify the function of the Glycine Receptor (GlyR).

Chemical Science published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C26H26N4O7, Application of 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Fang, Ge-min published the artcileA bright FIT-PNA hybridization probe for the hybridization state specific analysis of a CU RNA edit via FRET in a binary system, Name: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, the publication is Chemical Science (2018), 9(21), 4794-4800, database is CAplus and MEDLINE.

Given the length required for uniqueness of the targeted segment, the commonly used probes do not provide the level of sequence specificity needed to discriminate single base mismatched hybridization. Herein we introduce a binary probe system based on fluorescence resonance energy transfer (FRET) that distinguishes three possible states i.e. (i) absence of target, (ii) presence of edited (matched) and (iii) unedited (single base mismatched) target. To address the shortcomings of read-out via FRET, we designed donor probes that avoid bleed through into the acceptor channel and nevertheless provide a high intensity of FRET signaling. We show the combined use of thiazole orange (TO) and an oxazolopyridine analog (JO), linked as base surrogates in modified PNA FIT-probes that serve as FRET donor for a second, near-IR (NIR)-labeled strand. In absence of target, donor emission is low and FRET cannot occur in lieu of the lacking co-alignment of probes. Hybridization of the TO/JO-PNA FIT-probe with the (unedited RNA) target leads to high brightness of emission at 540 nm. Co-alignment of the NIR-acceptor strand ensues from recognition of edited RNA inducing emission at 690 nm. We show imaging of mRNA in fixed and live cells and discuss the homogeneous detection and intracellular imaging of a single nucleotide mRNA edit used by nature to post-transcriptionally modify the function of the Glycine Receptor (GlyR).

Chemical Science published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Name: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia