Tag: 100-200

Cavdar, Huseyin; Senturk, Murat; Guney, Murat; Durdagi, Serdar; Kayik, Gulru; Supuran, Claudiu T.; Ekinci, Deniz published an article in 2019, the title of the article was Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies.Synthetic Route of 626-48-2 And the article contains the following content:

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer’s disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Mol. docking and mol. dynamics (MD) simulations demonstrated the possible key interactions between the studied ligands and amino acid residues at different regions of the active sites of AChE and BuChE. Being diverse of the classical AChE and BuChE inhibitors, the investigated uracil derivatives may be used as lead mols. for designing new therapeutically effective enzyme inhibitors. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Synthetic Route of 626-48-2

The Article related to acetylcholinesterase butyrylcholinesterase inhibition uracil derivative, alzheimer’s disease, md simulations, acetylcholinesterase, butyrylcholinesterase, docking, inhibitor, uracil derivatives and other aspects.Synthetic Route of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cavdar, Huseyin; Senturk, Murat; Guney, Murat; Durdagi, Serdar; Kayik, Gulru; Supuran, Claudiu T.; Ekinci, Deniz published an article in 2019, the title of the article was Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies.Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione And the article contains the following content:

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer’s disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Mol. docking and mol. dynamics (MD) simulations demonstrated the possible key interactions between the studied ligands and amino acid residues at different regions of the active sites of AChE and BuChE. Being diverse of the classical AChE and BuChE inhibitors, the investigated uracil derivatives may be used as lead mols. for designing new therapeutically effective enzyme inhibitors. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

The Article related to acetylcholinesterase butyrylcholinesterase inhibition uracil derivative, alzheimer’s disease, md simulations, acetylcholinesterase, butyrylcholinesterase, docking, inhibitor, uracil derivatives and other aspects.Quality Control of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On May 1, 2016, Seiler, Vanessa Kristina; Huetzler, Wilhelm Maximilian; Bolte, Michael published an article.Synthetic Route of 4433-40-3 The title of the article was Eight new crystal structures of 5-(hydroxymethyl)uracil, 5-carboxyuracil and 5-carboxy-2-thiouracil: insights into the hydrogen-bonded networks and the predominant conformations of the C5-bound residues. And the article contained the following:

In order to examine the preferred hydrogen-bonding pattern of various uracil derivatives, namely 5-(hydroxymethyl)uracil, 5-carboxyuracil and 5-carboxy-2-thiouracil, and for a conformational study, crystallizationexperimentsyielded eight different structures: 5-(hydroxymethyl)uracil, C5H6N2O3, (I), 5-carboxyuracil-N,N-dimethylformamide (1/1), C5H4N2O4·C3H7NO, (II), 5-carboxyuracil-dimethyl sulfoxide (1/1), C5H4N2O4·C2H6OS, (III), 5-carboxyuracil-N,N-dimethylacetamide (1/1), C5H4N2O4·C4H9NO, (IV), 5-carboxy-2-thiouracil-N,N-dimethylformamide (1/1), C5H4N2O3S·C3H7NO, (V), 5-carboxy-2-thiouracil-dimethyl sulfoxide (1/1), C5H4N2O3S·C2H6OS, (VI), 5-carboxy-2-thiouracil-1,4-dioxane (2/3), 2C5H4N2O3S·3C6H12O3, (VII), and 5-carboxy-2-thiouracil, C10H8N4O6S2, (VIII). While the six solvated structures, i.e.(II)-(VII), contain intramol.S(6) O-H···O hydrogen-bond motifs between the carboxy and carbonyl groups, the usually favored R22(8) pattern between two carboxy groups is formed in the solvent-free structure, i.e.(VIII). Further R22(8) hydrogen-bond motifs involving either two N-H···O or two N-H···S hydrogen bonds were observedin three crystal structures, namely (I), (IV) and (VIII). In all eight structures, the residue at the ring 5-position shows a coplanar arrangement with respect to the pyrimidine ring which is in agreement with a search of the Cambridge Structural Database for six-membered cyclic compoundscontaininga carboxy group. The search confirmed that coplanarity between the carboxy group and the cyclic residue is strongly favored. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Synthetic Route of 4433-40-3

The Article related to hydroxymethyl carboxyuracil thiouracil carbon residue hydrogen bonding crystal structure, r22(8) patterns, cocrystals, crystal engineering, crystal structure, hydrogen bonds, uracil derivatives and other aspects.Synthetic Route of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On May 1, 2016, Kharlamova, Alexandra D.; Lushchekina, Sofya V.; Petrov, Konstantin A.; Kots, Ekaterina D.; Nachon, Florian; Villard-Wandhammer, Marielle; Zueva, Irina V.; Krejci, Eric; Reznik, Vladimir S.; Zobov, Vladimir V.; Nikolsky, Evgeny E.; Masson, Patrick published an article.Electric Literature of 626-48-2 The title of the article was Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment. And the article contained the following:

Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic anal. of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme·inhibitor complex (Ki=140 pM), an induced-fit step allows establishment of the final complex (Ki*=22 pM). The estimated koff is low, 0.05 min-1. On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki=1.77 μM; Ki’=3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution The complex is stabilized by cation-π, stacking and hydrogen-bonding interactions. Mol. dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a non-charged analog) to mouse and human AChEs were performed. Mol. modeling on mouse and human AChE showed that the slow step results from an enzyme conformational change that allows C-547 to cross the bottleneck in the active-site gorge, followed by formation of tight complex, as observed in the crystal structure. In contrast, the related non-charged compound C-35 is not a slow-binding inhibitor. It does not cross the bottleneck because it is not sensitive to the electrostatic driving force to reach the bottom of the gorge. Thus C-547 is one of the most potent and selective reversible inhibitors of AChE with a long residence time, τ=20 min, longer than for other reversible inhibitors used in the treatment of MG. This makes C-547 a promising drug for the treatment of this disease. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Electric Literature of 626-48-2

The Article related to myasthenia gravis acetylcholinesterase alkyl ammonium 6 methyl uracil, 6-methyluracil, x-ray structure, acetylcholinesterase, butyrylcholinesterase, molecular modelling, slow-binding inhibition and other aspects.Electric Literature of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Andre, Thierry; Saunders, Mark; Kanehisa, Akira; Gandossi, Eric; Fougeray, Ronan; Amellal, Nadia Causse; Falcone, Alfredo published an article in 2020, the title of the article was First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design.Electric Literature of 65-71-4 And the article contains the following content:

Trifluridine/tipiracil (TT) is an orally administered combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil hydrochloride, which increases the bioavailability of cytotoxic trifluridine. Encouraging antitumor activity of first-line TT + bevacizumab (TT-B) has been observed in a Phase II study in patients with unresectable metastatic colorectal cancer ineligible for combination oxaliplatin- or irinotecan-based therapy. Here, we describe the design of SOLSTICE (NCT03869892), an open-label, Phase III trial in unresectable metastatic colorectal cancer patients who are not candidates for, or do not require, intensive therapy. The 854 patients were randomized 1:1 to receive first-line TT-B vs. capecitabine + bevacizumab. The primary objective is to demonstrate superior progression-free survival with TT-B over capecitabine + bevacizumab. The first patient was enrolled in March 2019. Lay abstract : Trifluridine/tipiracil is an oral chemotherapy drug combination that acts by affecting the DNA of tumor cells. In a previous study, initial (first-line) treatment with trifluridine/tipiracil plus the tumor-starving (anti-angiogenic) drug bevacizumab was effective in patients with metastatic colorectal cancer that could not be surgically removed (i.e., was unresectable) and who could not receive intensive therapy. The SOLSTICE trial is designed to compare the efficacy and safety of first-line trifluridine/tipiracil + bevacizumab vs. another treatment, capecitabine + bevacizumab, in patients with unresectable metastatic colorectal cancer who are not candidates for intensive therapy. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Electric Literature of 65-71-4

The Article related to trifluridine tipiracil bevacizumab anticancer combination chemotherapy metastatic colorectal cancer, bevacizumab, capecitabine, first-line, metastatic colorectal cancer, trifluridine/tipiracil and other aspects.Electric Literature of 65-71-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Romeo, Roberto; Iannazzo, Daniela; Veltri, Lucia; Gabriele, Bartolo; Macchi, Beatrice; Frezza, Caterina; Marino-Merlo, Francesca; Giofre, Salvatore V. published an article in 2019, the title of the article was Pyrimidine 2,4-diones in the design of new HIV RT inhibitors.Recommanded Product: 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione And the article contains the following content:

The pyrimidine nucleus is a versatile core in the development of antiretroviral agents. On this basis, a series of pyrimidine-2,4-diones linked to an isoxazolidine nucleus have been synthesized and tested as nucleoside analogs, endowed with potential anti-HIV (human immunodeficiency virus) activity. Compounds 6a-c, characterized by the presence of an ethereal group at C-3, show HIV reverse transcriptase (RT) inhibitor activity in the nanomolar range as well as HIV-infection inhibitor activity in the low micromolar with no toxicity. In the same context, compound 7b shows only a negligible inhibition of RT HIV. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Recommanded Product: 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

The Article related to hiv infection lymphoblastoid cell reverse transcriptase inhibitor pyrimidine, hiv rt inhibitors, pyrimidine-2,4-dione derivatives, biological activity, molecular docking., reverse nucleosides and other aspects.Recommanded Product: 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On July 15, 2020, Ehlert, Christopher; Klamroth, Tillmann published an article.COA of Formula: C5H6N2O2 The title of the article was PSIXAS: A Psi4 plugin for efficient simulations of X-ray absorption spectra based on the transition-potential and Δ-Kohn-Sham method. And the article contained the following:

Near edge X-ray absorption fine structure (NEXAFS) spectra and their pump-probe extension (PP-NEXAFS) offer insights into valence- and core-excited states. We present PSIXAS, a recent implementation for simulating NEXAFS and PP-NEXAFS spectra by means of the transition-potential and the Δ-Kohn-Sham method. The approach is implemented in form of a software plugin for the Psi4 code, which provides access to a wide selection of basis sets as well as d. functionals. We briefly outline the theor. foundation and the key aspects of the plugin. Then, we use the plugin to simulate PP-NEXAFS spectra of thymine, a system already investigated by others and us. It is found that larger, extended basis sets are needed to obtain more accurate absolute resonance positions. We further demonstrate that, in contrast to ordinary NEXAFS simulations, where the choice of the d. functional plays a minor role for the shape of the spectrum, for PP-NEXAFS simulations the choice of the d. functional is important. Especially hybrid functionals (which could not be used straightforwardly before to simulate PP-NEXAFS spectra) and their amount of “Hartree-Fock like” exact exchange affects relative resonance positions in the spectrum. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).COA of Formula: C5H6N2O2

The Article related to x ray absorption spectra transition potential kohn sham, simulation x ray absorption spectra thymine, x-ray absorption, x-ray absorption spectroscopy, transition-potential method, δ-kohn-sham and other aspects.COA of Formula: C5H6N2O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Oh, Ki-Kwang; Adnan, Md.; Cho, Dong-Ha published an article in 2021, the title of the article was Network Pharmacology-Based Study to Uncover Potential Pharmacological Mechanisms of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) Flower against Cancer.Name: 6-Methylpyrimidine-2,4(1H,3H)-dione And the article contains the following content:

Cirsium japonicum var. maackii (Maxim.) Matsum. or Korean thistle flower is a herbal plant used to treat tumors in Korean folk remedies, but its essential bioactives and pharmacol. mechanisms against cancer have remained unexplored. This study identified the main compounds(s) and mechanism(s) of the C. maackii flower against cancer via network pharmacol. The bioactives from the C. maackii flower were revealed by gas chromatog.-mass spectrum (GC-MS), and SwissADME evaluated their physicochem. properties. Next, target(s) associated with the obtained bioactives or cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactives were visualized, constructed, and analyzed by RPackage. Finally, we implemented a mol. docking test (MDT) to explore key target(s) and compound(s) on AutoDockVina and LigPlot+. GC-MS detected a total of 34 bioactives and all were accepted by Lipinski′s rules and therefore classified as drug-like compounds (DLCs). A total of 597 bioactive-related targets and 4245 cancer-related targets were identified from public databases. The final 51 overlapping targets were selected between the bioactive targets network and cancer-related targets. With Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signaling pathways were manifested, and a hub signaling pathway (PI3K-Akt signaling pathway), a key target (Akt1), and a key compound (Urs-12-en-24-oic acid, 3-oxo, Me ester) were selected among the 20 signaling pathways via MDT. Overall, Urs-12-en-24-oic acid, 3-oxo, Me ester from the C. maackii flower has potent anti-cancer efficacy by inactivating Akt1 on the PI3K-Akt signaling pathway. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Name: 6-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to cirsium japonicum maackii flower plant extract cancer pharmacol, 3-oxo, akt1, c. maackii flower, pi3k-akt signaling pathway, urs-12-en-24-oic acid, cancer, methyl ester, network pharmacology and other aspects.Name: 6-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On May 31, 2022, Elloumi, Nesrine; Tahri, Safa; Fakhfakh, Raouia; Abida, Olfa; Mahfoudh, Nadia; Hachicha, Hend; Marzouk, Sameh; Bahloul, Zouhir; Masmoudi, Hatem published an article.Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was Role of innate immune receptors TLR4 and TLR2 polymorphisms in systemic lupus erythematosus susceptibility. And the article contained the following:

Through their recognition of various bacterial cell wall components, TLR2 and TLR4 participate in the innate response and modulate the activation of adaptive immunity. Therefore, the genetic background of these receptors might play a crucial role in autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated the possible association between polymorphisms within TLR2 and TLR4 genes with SLE susceptibility. A total of 100 SLE patients and 200 unrelated healthy controls of the Tunisian population were enrolled in the study. TLR4rs4986790, TLR4rs4986791, and TLR2rs5743708 genotyping were performed using a polymerase chain reaction-restriction fragment length polymorphism method. The number of guanine-thymine (GT) repeat microsatellite in the intron 2 of TLR2 gene was analyzed by sequencing. We reported a lack of allelic and genotypic association between SNPs of TLR4 and TLR2 genes and SLE pathogenesis. No correlation was found with any SLE features. However, SLE susceptibility was associated with the GT repeat microsatellite polymorphism in the human TLR2 gene. Further subclassification of alleles into three subclasses revealed a significant association between the long-sized repeats ((GT) >23) and SLE. Though the results showed the absence of genetic association of TLR4 and TLR2 SNPs with the risk of developing SLE, we have identified a protective association between the microsatellite polymorphism in intron 2 of the TLR2 gene and SLE. Functionally, these (GT)n repeats may confer modifying effects or susceptibility to certain inflammatory conditions. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to innate immune receptor systemic lupus erythematosus susceptibility, (gt) repeat microsatellite, tlr2 polymorphisms, tlr4 polymorphisms, innate immune receptors, systemic lupus erythematosus and other aspects.Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On March 15, 2018, Petrov, Konstantin; Zueva, Irina; Kovyazina, Irina; Sedov, Igor; Lushchekina, Sofya; Kharlamova, Alexandra; Lenina, Oksana; Koshkin, Sergei; Shtyrlin, Yurii; Nikolsky, Evgeny; Masson, Patrick published an article.Computed Properties of 626-48-2 The title of the article was C-547, a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase: Pharmacokinetic and pharmacodynamic studies. And the article contained the following:

C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was i.v. administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of distribution (3800 mL/kg) is 15 times larger than the distribution volume, indicating a good tissue distribution. C-547 is slowly eliminated (kel = 0.17 h-1; T1/2 = 4 h) from the bloodstream. Effect of C-547 on animal model of myasthenia gravis persists for more than 72 h, even though the drug is not anal. detectable in the blood. A PK/PD model was built to account for such a pharmacodynamical (PD) effect. Long-lasting effect results from micro-PD mechanisms: the slow-binding nature of inhibition, high affinity for AChE and long residence time on target at neuromuscular junction (NMJ). In addition, NMJ spatial constraints i.e. high concentration of AChE in a small volume, and slow diffusion rate of free C-547 out of NMJ, make possible effective rebinding of ligand. Thus, compared to other cholinesterase inhibitors used for palliative treatment of myasthenia gravis, C-547 is the most selective drug, displays a slow pharmacokinetics, and has the longest duration of action. This makes C-547 a promising drug leader for treatment of myasthenia gravis, and a template for development of other drugs against neurol. diseases and for neuroprotection. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Computed Properties of 626-48-2

The Article related to myasthenia gravis c547 pharmacodynamics pharmacokinetics acetylcholinesterase, 6-methyluracil, acetylcholinesterase, binding kinetics, myasthenia gravis, pharmacodynamics, pharmacokinetics and other aspects.Computed Properties of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia