Category: pyrimidines

Dracinsky, Martin published the artcileMechanism of the Isotopic Exchange Reaction of the 5-H Hydrogen of Uracil Derivatives in Water and Nonprotic Solvents, Name: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is European Journal of Organic Chemistry (2011), 777-785, S777/1-S777/16, database is CAplus.

The mechanism of the isotopic exchange reaction of the 5-H hydrogen of uracil and its Me derivatives in water and organic solvents has been studied. The key intermediate of the reaction is a C-5 tautomer of uracil in which the carbon atom at the 5-position has two hydrogen atoms, its hybridization is changed from sp² to sp³, and the aromaticity of the pyrimidine ring is lost. We have used ¹H NMR spectroscopy to follow the kinetics of the hydrogen/deuterium exchange reaction. In aqueous media a general base catalysis was observed and for exchange in organic solvents we have proposed a reaction mechanism that involves the participation of solvent mols. The reaction rates determined by NMR can be rationalized by d. functional computations. We have shown that the hydrogen-to-deuterium exchange reaction is much faster in some suitable nucleophilic solvents than in water. These findings could be used for the tritium labeling of pyrimidine nucleic acid bases.

European Journal of Organic Chemistry 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 C5H6N2O2, Name: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Dracinsky, Martin published the artcileIsotope exchange reactions of the hydrogen H-5 of selected pyrimidine derivatives and the preparation of tritium-labeled pyrimidines, Product Details of C5H6N2O2, the publication is Collection of Czechoslovak Chemical Communications (2011), 76(12), 1567-1577, database is CAplus.

The hydrogen-to-deuterium isotope exchange reaction of hydrogen in position 5 of pyrimidine derivatives was studied using NMR techniques. The dependence of the reaction rate on the pH and on the solvent composition was explored. In tracer experiments using tritiated water, the application of this exchange reaction was tested for the preparation of pyrimidine derivatives labeled by tritium.

Collection of Czechoslovak Chemical Communications 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 C5H6N2O2, Product Details of C5H6N2O2.

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

Joshi, Rajendra published the artcileFacile synthesis of peptide nucleic acids and peptide nucleic acid-peptide conjugates on an automated peptide synthesizer, Related Products of pyrimidines, the publication is Journal of Peptide Science (2011), 17(1), 8-13, database is CAplus and MEDLINE.

Peptide nucleic acids (PNAs) are DNA mimics with a neutral peptide backbone instead of the neg. charged sugar phosphates. PNAs exhibit several attractive features such as high chem. and thermal stability, resistance to enzymic degradation, and stable binding to their RNA or DNA targets in a sequence-specific manner. Therefore, they are widely used in mol. diagnosis of antisense-targeted therapeutic drugs or probes and in pharmaceutical applications. However, the main hindrance to the effective use of PNAs is their poor uptake by cells as well as the difficult and laborious chem. synthesis. In order to achieve an efficient delivery of PNAs into cells, there are already many published reports of peptides being used for transport across the cell membrane. In this protocol, the authors describe the automated as well as cost-effective semi-automated synthesis of PNAs and PNA-peptide constructs on an automated peptide synthesizer. The facile synthesis of PNAs will be helpful in generating PNA libraries usable, e.g. for high-throughput screening in biomol. studies. Efficient synthetic schemes, the automated procedure, the reduced consumption of costly reagents, and the high purity of the products are attractive features of the reported procedure. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

Journal of Peptide 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, Related Products of pyrimidines.

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

Paudler, William W. published the artcileBromination of some pyridine and diazine N-oxides, SDS of cas: 31401-45-3, the publication is Journal of Organic Chemistry (1983), 48(7), 1064-9, database is CAplus.

Selected monosubstituted pyridines, pyrazines, pyrimidines, and their N-oxides, having an electron-donating substituent, were successfully brominated under very mild conditions. The N-oxide function itself is not sufficient to cause these π-deficient systems to undergo electrophilic aromatic halogenation. Only strongly electron-donating substituents (amino groups) activate the heterocyclic nucleus toward bromination. These substituents direct the electrophilic substitution ortho/para to them with or without the N-oxide group present. Pyridine and diazines with moderately activating substituents such as alkoxy groups are brominated only when their ortho/para activation is augmented by the activation of the N-oxide function. Failure to brominate 5-methoxypyrimidine 1-oxide may well reflect the greater π deficiency of the pyrimidine ring.

Journal of Organic Chemistry 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 C6H9N3, SDS of cas: 31401-45-3.

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

Kolman, Viktor published the artcileInfluence of the C-5 substitution in polysubstituted pyrimidines on inhibition of prostaglandin E₂ production, Related Products of pyrimidines, the publication is European Journal of Medicinal Chemistry (2018), 295-301, database is CAplus and MEDLINE.

As a part of a broader structure-activity relationship study of substituted 2-aminopyrimidines, the influence of the C-5 substitution on inhibition of prostaglandin E2 (PGE2) production was studied. Thirty compounds were prepared starting from the corresponding 2-amino-4,6-dichloropyrimidines using Suzuki cross-coupling. It was shown previously that 2-amino-4,6-dichloropyrimidines with smaller C-5 substituent (hydrogen and methyl) were devoid of significant activity, while 5-Bu derivatives exhibited prominent potency. In this study, on the other hand, both monoaryl- and bisarylpyrimidines were potent inhibitors of PGE2 production regardless the length of the C-5 substituent (hydrogen, Me, n-butyl). Moreover, the shorter the C-5 substituent the higher potency to inhibit PGE₂ production was observed 2-Amino-4,6-diphenylpyrimidine was the best inhibitor of PGE2 production with IC₅₀ = 3 nM and no cytotoxicity. The most potent inhibitors deserve further preclin. evaluation as potential anti-inflammatory agents.

European Journal of Medicinal Chemistry 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, Related Products of pyrimidines.

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

Aiba, Yuichiro published the artcilePNA-NLS conjugates as single-molecular activators of target sites in double-stranded DNA for site-selective scission, Recommanded Product: 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 Organic & Biomolecular Chemistry (2013), 11(32), 5233-5238, database is CAplus and MEDLINE.

Artificial DNA cutters have been developed by us in our previous studies by combining two strands of pseudo-complementary peptide nucleic acid (pcPNA) with Ce(iv)-EDTA-promoted hydrolysis. The pcPNAs have two modified nucleobases (2,6-diaminopurine and 2-thiouracil) instead of conventional A and T, and can invade double-stranded DNA to activate the target site for the scission. This system has been applied to site-selective scissions of plasmid, λ-phage, E. coli genomic DNA, and human genomic DNA. Here, we have reported a still simpler and more convenient DNA cutter obtained by conjugating peptide nucleic acid (PNA) with a nuclear localization signal (NLS) peptide. This new DNA cutter requires only one PNA strand (instead of two) bearing conventional (non-pseudo-complementary) nucleobases. This PNA-NLS conjugate effectively activated the target site in double-stranded DNA and induced site-selective scission by Ce(iv)-EDTA. The complex formation between the conjugate and DNA was concretely evidenced by spectroscopic results based on time-resolved fluorescence. The target scission site of this new system was straightforwardly determined by the Watson-Crick base pairing rule, and mismatched sequences were clearly discriminated. Importantly, even highly GC-rich regions, which are difficult to be targeted by a previous strategy using pcPNA, were successfully targeted. All these features of the present DNA cutter make it promising for various future applications.

Organic & Biomolecular Chemistry 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, Recommanded Product: 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

Aiba, Yuichiro published the artcilePNA-NLS conjugates as single-molecular activators of target sites in double-stranded DNA for site-selective scission, Product Details of C39H35N5O8, the publication is Organic & Biomolecular Chemistry (2013), 11(32), 5233-5238, database is CAplus and MEDLINE.

Artificial DNA cutters have been developed by us in our previous studies by combining two strands of pseudo-complementary peptide nucleic acid (pcPNA) with Ce(iv)-EDTA-promoted hydrolysis. The pcPNAs have two modified nucleobases (2,6-diaminopurine and 2-thiouracil) instead of conventional A and T, and can invade double-stranded DNA to activate the target site for the scission. This system has been applied to site-selective scissions of plasmid, λ-phage, E. coli genomic DNA, and human genomic DNA. Here, we have reported a still simpler and more convenient DNA cutter obtained by conjugating peptide nucleic acid (PNA) with a nuclear localization signal (NLS) peptide. This new DNA cutter requires only one PNA strand (instead of two) bearing conventional (non-pseudo-complementary) nucleobases. This PNA-NLS conjugate effectively activated the target site in double-stranded DNA and induced site-selective scission by Ce(iv)-EDTA. The complex formation between the conjugate and DNA was concretely evidenced by spectroscopic results based on time-resolved fluorescence. The target scission site of this new system was straightforwardly determined by the Watson-Crick base pairing rule, and mismatched sequences were clearly discriminated. Importantly, even highly GC-rich regions, which are difficult to be targeted by a previous strategy using pcPNA, were successfully targeted. All these features of the present DNA cutter make it promising for various future applications.

Organic & Biomolecular Chemistry 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, Product Details of C39H35N5O8.

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

Kaczanowska, Katarzyna published the artcileStructural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein, SDS of cas: 56-05-3, the publication is Proceedings of the National Academy of Sciences of the United States of America (2014), 111(29), 10749-10754, database is CAplus and MEDLINE.

The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homol. model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different mol. variants exhibiting pos., nH > 1.0, and neg. cooperativity, nH < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of mols. bind at the agonist-antagonist site, as expected from their competition with epibatidine. An anal. of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Pos. and neg. cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes.

Proceedings of the National Academy of Sciences of the United States of America 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, SDS of cas: 56-05-3.

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

Ren, Sijin published the artcileAn EOM-CCSD-PCM Benchmark for Electronic Excitation Energies of Solvated Molecules, Related Products of pyrimidines, the publication is Journal of Chemical Theory and Computation (2017), 13(1), 117-124, database is CAplus and MEDLINE.

In this work, we benchmark the equation of motion coupled cluster with single and double excitations (EOM-CCSD) method combined with the polarizable continuum model (PCM) for the calculation of electronic excitation energies of solvated mols. EOM-CCSD is one of the most accurate methods for computing one-electron excitation energies, and accounting for the solvent effect on this property is a key challenge. PCM is one of the most widely employed solvation models due to its adaptability to virtually any solute and its efficient implementation with d. functional theory methods (DFT). Our goal in this work is to evaluate the reliability of EOM-CCSD-PCM, especially compared to time-dependent DFT-PCM (TDDFT-PCM). Comparisons between calculated and exptl. excitation energies show that EOM-CCSD-PCM consistently overestimates exptl. results by 0.4-0.5 eV, which is larger than the expected EOM-CCSD error in vacuo. We attribute this decrease in accuracy to the approximated solvation model. Thus, we investigate a particularly important source of error: the lack of H-bonding interactions in PCM. We show that this issue can be addressed by computing an energy shift, Δ_HB, from bare-PCM to microsolvation + PCM at DFT level. Our results show that such a shift is independent of the functional used, contrary to the absolute value of the excitation energy. Hence, we suggest an efficient protocol where the EOM-CCSD-PCM transition energy is corrected by Δ_HB(DFT), which consistently improves the agreement with the exptl. measurements.

Journal of Chemical Theory and Computation 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 C5H6N2O2, Related Products of pyrimidines.

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

Xu, Li published the artcileSynthesis, Structure-Activity Relationships, and In Vivo Evaluation of Novel Tetrahydropyran-Based Thiodisaccharide Mimics as Galectin-3 Inhibitors, Formula: C7H6N2O, the publication is Journal of Medicinal Chemistry (2021), 64(10), 6634-6655, database is CAplus and MEDLINE.

Galectin-3 is a member of a family of β-galactoside-binding proteins. A substantial body of literature reports that galectin-3 plays important roles in cancer, inflammation, and fibrosis. Small-mol. galectin-3 inhibitors, which are generally lactose or galactose-based derivatives, have the potential to be valuable disease-modifying agents. In our efforts to identify novel galectin-3 disaccharide mimics to improve drug-like properties, we found that one of the monosaccharide subunits can be replaced with a suitably functionalized tetrahydropyran ring. Optimization of the structure-activity relationships around the tetrahydropyran-based scaffold led to the discovery of potent galectin-3 inhibitors. Three compounds (identified within) were selected for further in vivo evaluation. The synthesis, structure-activity relationships, and in vivo evaluation of novel tetrahydropyran-based galectin-3 inhibitors are described.

Journal of Medicinal Chemistry published new progress about 1059705-07-5. 1059705-07-5 belongs to pyrimidines, auxiliary class Pyrimidine, name is 5-Ethynyl-2-methoxypyrimidine, and the molecular formula is C4H4OS, Formula: C7H6N2O.

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