Day: November 21, 2022

Wang, Zhisong published the artcileStructure-Based Design of Highly Potent Toll-like Receptor 7/8 Dual Agonists for Cancer Immunotherapy, Name: 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, the publication is Journal of Medicinal Chemistry (2021), 64(11), 7507-7532, database is CAplus and MEDLINE.

Design and synthesis of a series of pyrido[3,2-d]pyrimidine-based toll-like receptor 7/8 dual agonists, e.g., I that exhibited potent and near-equivalent agonistic activities toward TLR7 and TLR8. In vitro, compounds significantly induced the secretion of IFN-α, IFN-γ, TNF-α, IL-1β, IL-12p40, and IP-10 in human peripheral blood mononuclear cell assays. In vivo, compounds significantly suppressed tumor growth in CT26 tumor-bearing mice by remodeling the tumor microenvironment. Addnl., compounds markedly improved the antitumor activity of PD-1/PD-L1 blockade. These results demonstrated that TLR7/8 agonists held great potential as single agents or in combination with PD-1/PD-L1 blockade for cancer immunotherapy.

Journal of Medicinal Chemistry published new progress about 897359-74-9. 897359-74-9 belongs to pyrimidines, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine,Amide, name is 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one, and the molecular formula is C14H20BNO3, Name: 2-Amino-6-chloropyrido[3,2-d]pyrimidin-4(1H)-one.

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

Burrow, P. D. published the artcileVibrational Feshbach resonances in uracil and thymine, Formula: C5H6N2O2, the publication is Journal of Chemical Physics (2006), 124(12), 124310/1-124310/7, database is CAplus and MEDLINE.

Sharp peaks in the dissociative electron attachment (DEA) cross sections of uracil and thymine at energies below 3 eV are assigned to vibrational Feshbach resonances (VFRs) arising from coupling between the dipole bound state and the temporary anion state associated with occupation of the lowest σ^* orbital. Three distinct vibrational modes are identified, and their presence as VFRs is consistent with the amplitudes and bonding characteristics of the σ^* orbital wave function. A deconvolution method is also employed to yield higher effective energy resolution in the DEA spectra. The site dependence of DEA cross sections is evaluated using Me substituted uracil and thymine to block H atom loss selectively. Implications for the broader issue of DNA damage are briefly discussed.

Journal of Chemical Physics 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, Formula: C5H6N2O2.

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

Chantell, Christina A. published the artcileLow-cost, automated synthesis of a PNA-peptide conjugate on a peptide synthesizer, 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 American Biotechnology Laboratory (2009), 27(8), 8-10, database is CAplus.

Two peptide nucleic acid (PNA) sequences, one containing a lysine residue at the C-terminus and the other containing a peptide analog of LH-releasing hormone, were synthesized in an automated peptide synthesizer. The PNA sequence was constructed from protected monomers, Fmoc-A(Bhoc)aeg-OH, Fmoc-C(Bhoc)aeg-OH, Fmoc-G(Bhoc)aeg-OH and Fmoc-T-aeg-OH, which were coupled to Fmoc-Lys(Boc)-Wang resin using HATU as a coupling reagent. This work demonstrated the successful automated synthesis of a PNA sequence and a PNA-peptide conjugate on “Prelude” automated peptide synthesizer which enabled minimizing overall consumption and costs.

American Biotechnology Laboratory 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

Gebauer, Sabine published the artcileHigh performance liquid chromatography on calixarene-bonded silica gels. II. Separations of regio- and stereoisomers on p-tert-butylcalix[n]arene phases, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of Chromatographic Science (1998), 36(8), 383-387, database is CAplus.

The chromatog. behavior of new calix[n]arene-bonded (n = 4, 6, 8) silica gels are described. Cavities of different size and shape are formed depending on the number of aromatic moieties. The differences in ring size were used to study chromatog. selectivities towards analytes of various substance classes, including disubstituted aromatics, uracil derivatives, and estradiol epimers. The authors’ results indicate that these calixarene-bonded phases show a high resolution power for regio- and stereoisomers.

Journal of Chromatographic Science 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, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Mueller, Andreas published the artcileProbing the Watson-Crick, Wobble, and Sugar-Edge Hydrogen Bond Sites of Uracil and Thymine, Computed Properties of 608-34-4, the publication is Journal of Physical Chemistry A (2005), 109(23), 5055-5063, database is CAplus and MEDLINE.

The nucleobases uracil (U) and thymine (T) offer three hydrogen-bonding sites for double H-bond formation via neighboring N-H and C:O groups, giving rise to the Watson-Crick, wobble and sugar-edge hydrogen bond isomers. The hydrogen bond properties of all three sites by forming hydrogen bonded dimers of U, 1-methyluracil (1MU), 3-methyluracil (3MU), and T with 2-pyridone (2PY) are probed. The mass- and isomer-specific S₁ ← S₀ vibronic spectra of 2PY·U, 2PY·3MU, 2PY·1MU, and 2PY·T were measured using UV laser resonant two-photon ionization (R2PI). The spectra of the Watson-Crick and wobble isomers of 2PY·1MU were separated using UV-UV spectral hole-burning. The different isomers are identified by combining three different diagnostic tools: (1) Selective methylation of the uracil N3-H group, which allows formation of the sugar-edge isomer only, and methylation of the N1-H group, which leads to formation of the Watson-Crick and wobble isomers. (2) The exptl. S₁ ← S₀ origins exhibit large spectral blue shifts relative to the 2PY monomer. Ab initio CIS calculations of the spectral shifts of the different hydrogen-bonded dimers show a linear correlation with experiment This correlation allows the identification of the R2PI spectra of the weakly populated Watson-Crick and wobble isomers of both 2PY·U and 2PY·T. (3) PW91 d. functional calculation of the ground-state binding and dissociation energies D_e and D₀ are in agreement with the assignment of the dominant hydrogen bond isomers of 2PY·U, 2PY·3MU and 2PY·T as the sugar-edge form. For 2PY·U, 2PY·T and 2PY·1MU the measured wobble:Watson-Crick:sugar-edge isomer ratios are in good agreement with the calculated ratios, based on the ab initio dissociation energies and gas-phase statistical mechanics. The Watson-Crick and wobble isomers are thereby determined to be several kcal/mol less strongly bound than the sugar-edge isomers. The 36 observed intermol. frequencies of the nine different H-bonded isomers give detailed insight into the intermol. force field.

Journal of Physical Chemistry A 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, Computed Properties of 608-34-4.

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

Chu, Te-Wei published the artcileHybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation, Quality Control of 186046-81-1, the publication is Journal of Controlled Release (2015), 220(Part_B), 608-616, database is CAplus and MEDLINE.

This work presents a new concept in hybrid hydrogel design. Synthetic water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) polymers grafted with multiple peptide nucleic acids (PNAs) are crosslinked upon addition of the linker DNA. The self-assembly is mediated by the PNA-DNA complexation, which results in the formation of hydrophilic polymer networks. We show that the hydrogels can be produced through two different types of complexations. Type I hydrogel is formed via the PNA/DNA double-helix hybridization. Type II hydrogel utilizes a unique “P-form” oligonucleotide triple-helix that comprises two PNA sequences and one DNA. Microrheol. studies confirm the resp. gelation processes and disclose a higher critical gelation concentration for the type I gel when compared to the type II design. SEM reveals the interconnected microporous structure of both types of hydrogels. Type I double-helix hydrogel exhibits larger pore sizes than type II triple-helix gel. The latter apparently contains denser structure and displays greater elasticity as well. The designed hybrid hydrogels have potential as novel biomaterials for pharmaceutical and biomedical applications.

Journal of Controlled Release 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, Quality Control of 186046-81-1.

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

Chu, Te-Wei published the artcileHybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation, Related Products of pyrimidines, the publication is Journal of Controlled Release (2015), 220(Part_B), 608-616, database is CAplus and MEDLINE.

This work presents a new concept in hybrid hydrogel design. Synthetic water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) polymers grafted with multiple peptide nucleic acids (PNAs) are crosslinked upon addition of the linker DNA. The self-assembly is mediated by the PNA-DNA complexation, which results in the formation of hydrophilic polymer networks. We show that the hydrogels can be produced through two different types of complexations. Type I hydrogel is formed via the PNA/DNA double-helix hybridization. Type II hydrogel utilizes a unique “P-form” oligonucleotide triple-helix that comprises two PNA sequences and one DNA. Microrheol. studies confirm the resp. gelation processes and disclose a higher critical gelation concentration for the type I gel when compared to the type II design. SEM reveals the interconnected microporous structure of both types of hydrogels. Type I double-helix hydrogel exhibits larger pore sizes than type II triple-helix gel. The latter apparently contains denser structure and displays greater elasticity as well. The designed hybrid hydrogels have potential as novel biomaterials for pharmaceutical and biomedical applications.

Journal of Controlled Release 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, Related Products of pyrimidines.

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

Gambacorta, Augusto published the artcileHSAB driven chemoselectivity in alkylation of uracil derivatives. A high yielding preparation of 3-alkylated and unsymmetrically 1,3-dialkylated uracils, Name: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Tetrahedron (1999), 55(43), 12615-12628, database is CAplus.

A qual. hardness scale (N¹<N³<O⁴) has been found for the conjugated bases of 2-methoxy-4(3H)-pyrimidinone and its 5- and 6-Me derivatives and applied to high yielding chemoselective N³ methylation, ethylation and benzylation reactions. Removal of the 2-methoxy group followed by a second alkylation affords unsym. 1,3-disubstituted uracils.

Tetrahedron 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

Shen, Gang published the artcilePhospholipid Conjugate for Intracellular Delivery of Peptide Nucleic Acids, SDS of cas: 186046-81-1, the publication is Bioconjugate Chemistry (2009), 20(9), 1729-1736, database is CAplus and MEDLINE.

Peptide nucleic acids (PNAs) have a number of attractive features that have made them an ideal choice for antisense and antigene-based tools, probes, and drugs, but their poor membrane permeability has limited their application as therapeutic or diagnostic agents. Herein, we report a general method for the synthesis of phospholipid-PNAs (LP-PNAs) and compare the effect of noncleavable lipids and bioreductively cleavable lipids (L and LSS) and phospholipid (LP) on the splice-correcting bioactivity of a PNA bearing the cell penetrating Arg9 group (PNA-R9). While the three constructs show similar and increasing bioactivity at 1-3 μM, the activity of LP-PNA-R9 continues to increase from 4-6 μM, while the activity of L-PNA-R9 remains constant and that of LSS-PNA-R9 decreases rapidly in parallel with their relative cytotoxicity. The activity of both LP-PNA-R9 and L-PNA-R9 dramatically increased in the presence of chloroquine, as expected for an endocytic entry mechanism. The constructs were also found to have CMC values of 1.0 and 4.5 μM, resp., in 150 mM NaCl, pH 7 water, suggesting that micelle formation may play a hitherto unrecognized role in modulating toxicity and/or facilitating endocytosis.

Bioconjugate 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 C6H4ClNO2, SDS of cas: 186046-81-1.

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

Mastryukov, Vladimir S. published the artcileThe effect of methylation on the structure of uracil, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Journal of Molecular Structure (1995), 173-86, database is CAplus.

Equilibrium geometries of uracil, 1-methyluracil and 3-methyluracil (in which the Me group is attached to nitrogen), 5-methyluracil (thymine) and 6-methyluracil (in which the Me group is attached to carbon), 1,3-dimethyluracil and 5,6-dimethyluracil have been determined by ab initio Hartree-Fock calculations with the split-valence 4-21G basis set. For the methylated derivatives, calculations are made for different conformations corresponding to different orientations of the Me groups. The conformational energy differences are small, indicating a very low barrier to internal rotation, except for 5- and 6-methyluracils in which there is a preference of 1-2kcalmol^-1 for the conformer with the Me C-H bond eclipsing the double bond of the ring. The structural differences between the methylated uracils and the parent mol. are analyzed. Angular deformations within the ring induced by substitution of a Me group for hydrogen follow, to a rough approximation, the trends established earlier for benzene derivatives on the basis of X-ray studies. Deviations occur due to the difference between nitrogen and carbon in the ring, with deformations being more pronounced for N- than for C-substituted uracils. The Me groups, in general, show a distinct tilt away from an adjacent carbonyl group, indicating a repulsive interaction. Mulliken population anal. shows the electroneg. Me group withdraws charge mainly from the atom to which it is attached and, to at least as great an extent, from the adjacent ring atoms. The results are compared with those obtained earlier by the semiempirical MINDO/3 method and also by different exptl. techniques including X-ray, neutron, and electron diffraction. These other studies have given much information on the structure of the compounds, but because of their nature they have not been able to analyze detailed structural variations induced by the Me group substitution.

Journal of Molecular Structure 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, Safety of 3-Methylpyrimidine-2,4(1H,3H)-dione.

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