Month: November 2022

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

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

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

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

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

Li, Wu-Hu published the artcileIn-Situ Infrared Spectroscopic and Scanning Tunneling Microscopy Investigations of the Chemisorption Phases of Uracil, Thymine, and 3-Methyl Uracil on Au(111) Electrodes, Category: pyrimidines, the publication is Langmuir (1999), 15(14), 4875-4883, database is CAplus.

The complementary techniques of in-situ IR spectroscopy and scanning tunneling microscopy (STM) have been used in this study to build detailed structural models for the chemisorbed forms of uracil, thymine, and 3-Me uracil on Au(111) electrodes. The IR spectra, in water and D₂O electrolytes, show that both uracil and thymine adopt similar coordination forms with the surface with both exocyclic oxygen atoms and a deprotonated N3 facing in toward the surface in a vertically oriented chemisorbate. 3-Me uracil cannot exhibit such a surface coordination and its IR signature in the carbonyl stretching region is quite different. This is interpreted as the chemisorbate interacting through its deprotonated N1 and C2=O. STM has been used to characterize and compare the mol. ordering of the three resp. adsorbates. Uracil exhibits the highest coverage structure c(3x√3), while thymine exhibits smaller ordered domains which are expanded in one direction to allow for the spatial requirements of the Me group on thymine. The domain size for the thymine chemisorbate could be improved by temperature annealing the electrode in-situ and a “pseudo c(√3×4)” structure was observed Both the uracil and thymine chemisorbate structures feature chains of mols., stacked like “rolls of coins”, close enough for-stacking to occur. The structure of thymine overlayers differs from uracil, since there are a number of different possible orientations of adjacent mol. rows, which results in a high frequency of stacking faults. These differences are discussed. 3-Me uracil is quite different, exhibiting a rather low coverage, albeit a highly ordered structure (5×2√3) which cannot allow-stacking. On the basis of these observations, the factors governing the formation of the resp. chemisorbed phases are discussed.

Langmuir 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, Category: pyrimidines.

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

Zengeya, Thomas published the artcileTriple-Helical Recognition of RNA Using 2-Aminopyridine-Modified PNA at Physiologically Relevant Conditions, COA of Formula: C26H26N4O7, the publication is Angewandte Chemie, International Edition (2012), 51(50), 12593-12596, database is CAplus and MEDLINE.

It was recently proposed that biol. relevant double-stranded RNAs (dsRNAs) could be recognized by major groove-binding peptide nucleic acids (PNAs), resulting in triple-helix formation. The present work demonstrates that sequence-selective recognition of duplex RNA can be achieved under physiol. relevant conditions by PNAs containing 2-aminopyridine (M). After preliminary studies that confirmed the binding of M-modified PNAs to RNA hairpin structures, pri-miRNA-215 was selected as an example of a biol. relevant RNA duplex for binding studies with M-modified PNA. Using an RNA hairpin model that contains the purine-rich recognition site present in pri-miRNA-215, it was shown that a PNA containing three M bases recognized the model hairpin with high affinity and 1:1 stoichiometry.

Angewandte Chemie, International Edition 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 C12H10F2Si, COA of Formula: C26H26N4O7.

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

Chen, Yunan published the artcileAn experimental investigation of sewage sludge gasification in near and super-critical water using a batch reactor, Computed Properties of 31401-45-3, the publication is International Journal of Hydrogen Energy (2013), 38(29), 12912-12920, database is CAplus.

The gasification of sewage sludge in near and super-critical water was investigated in a batch reactor. Results showed that the formation of gaseous products could be intensively affected by temperature In order to understand the effect of temperature on the development of reaction process and the formation of gaseous products better, the detailed characteristics of solid and liquid products were analyzed by SEM, N₂ adsorption-desorption technique, FTIR, TOC, Ammonia-nitrogen anal. and SPE-GC/MS. The changes in the yield distribution of products and the characteristics of solid and liquid products indicated that organic matters in sewage sludge were almost completely dissolved and hydrolyzed in water at 425 °C. The dissolution and hydrolysis products were gasified by reforming and other reactions. The polymerization and dehydrogenation also occurred in dissolution and hydrolysis products, and the Diels-Alder reaction mechanism could be used to explain the phenomenon.

International Journal of Hydrogen Energy 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, Computed Properties of 31401-45-3.

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

Bayramoglu, Duygu published the artcileAn Efficient Synthetic Method for the Synthesis of Novel Pyrimido[1,2-a]Pyrimidine-3-Carboxylates: Comparison of Irradiation and Conventional Conditions, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Polycyclic Aromatic Compounds, database is CAplus.

A very simple and efficient procedure for the synthesis of novel pyrimido[1,2-a]pyrimidine derivatives was described. Thermal cyclization reactions of 2-aminopyrimidine and its substituted derivatives with di-Et ethoxymethylenemalonate (EMME) was investigated. Conventional heating and microwave irradiation (MW) conditions were applied to enable the comparison of both techniques on the obtained products. Besides the effect of different reaction parameters and the substituents on the conversion reactions was also investigated in detail. Structural analyses of all compounds synthesized with high yields was carried out by suitable spectroscopic methods (FT-IR, NMR, mass spectroscopy, LC-MS TOF).

Polycyclic Aromatic Compounds 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, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

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

Motloch, Petr published the artcileTriaminopyrimidine derivatives as transmembrane HCl transporters, SDS of cas: 56-05-3, the publication is Organic & Biomolecular Chemistry (2019), 17(22), 5633-5638, database is CAplus and MEDLINE.

Small synthetic mols. capable of inducing transmembrane anion transport have received a lot of attention as potential anti-cancer agents due to their ability to interfere with intracellular pH homeostasis. A series of triaminopyrimidine-based anion transporters have been synthesized, and they are found to diminish proton gradients across lipid bilayers at physiol. relevant pH. The compounds have pK_a values (≈7.2) that allow protonation/deprotonation processes coupled with anion binding/unbinding events in physiol. relevant conditions. Synthetic vesicle transport experiments as well as solid state structures indicate synergistic binding of HCl. Cell assays show that the transporters induce apoptosis in various cancerous cell lines.

Organic & Biomolecular 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, SDS of cas: 56-05-3.

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