Month: November 2022

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

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

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

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

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

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

On January 28, 2010, Bury, Michael Jonathan; Cheung, Mui; Eidam, Hilary Schenck; Fox, Ryan Michael; Goodman, Krista; Manas, Eric Steven published a patent.SDS of cas: 85386-20-5 The title of the patent was Preparation of diazabicycloheptyl amino acid derivatives as transient receptor potential channel TRPV4 antagonists. And the patent contained the following:

Title compounds I [R1′ = (R1)i; i = 0-3; R1 = alkyl, alkoxy, CF3, halo, OCF3, CN, etc.; R2 = alkyl, cycloalkylmethyl, benzyl; R3 = (un)substituted pyrrolyl, pyrazolyl, tetrazolyl, isoquinolinyl,pyrimidinyl, etc.; ; G = (S,S)- or (R,R)-2,5-diazabicycloheptyl; X = a bond, CH2; Y = NH, N-alkyl, S; R5 = H, alkyl; and their pharmaceutically acceptable salts], were prepared Thus, a 5-step synthesis using 1,1-dimethylethyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate, 3-methyl-N-[[(phenylmethyl)oxy]carbonyl]-L-valine, and 1H-indole-2-carboxylic acid gave II. Tested title compounds inhibited TRPV4 with IC50 in the range of 1 nM to 10 μM. The experimental process involved the reaction of 5-Phenylpyrimidine-2-carboxylic acid(cas: 85386-20-5).SDS of cas: 85386-20-5

The Article related to diazabicycloheptylaminoacid preparation transient receptor potential channel trpv4 antagonist, overactive bladder pain cardiovascular disease arthritis treatment diazabicycloheptane preparation and other aspects.SDS of cas: 85386-20-5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On October 31, 2021, An, Tingting; Chen, Mengxue; Zu, Zhongqi; Chen, Qi; Lu, Hengqian; Yue, Pengxiang; Gao, Xueling published an article.Recommanded Product: 4433-40-3 The title of the article was Untargeted and targeted metabolomics reveal changes in the chemical constituents of instant dark tea during liquid-state fermentation by Eurotium cristatum. And the article contained the following:

Instant green tea powder was used as raw material to prepare an instant dark tea via liquid-state fermentation by Eurotium cristatum. To understand how the chem. constituents present in fermented green tea develop during fermentation, samples were collected on different days during fermentation for qual. analyses by ultra-performance liquid chromatog.-Q Exactive Orbitrap/Mass spectrometry. Untargeted metabolomics analyses revealed that the levels of original secondary metabolites in the instant green tea changed significantly from day 3 to day 5 during fermentation Targeted metabolomics indicated that the levels of galloylated catechins (GCs) and free amino acids (FAAs) significantly decreased, but the nongalloylated catechins (NGCs), alkaloids, thearubigins and theabrownins increased dramatically after fermentation The changes in the contents of catechins, gallic acid and free amino acids in the instant dark tea samples were pos. related to the DPPH radical scavenging activities in vitro, and the phenolic acids and FAAs were pos. related to the inhibitory effects towards α-glucosidase. These results showed that fermentation by Eurotium cristatum is critical to the formation of certain qualities of instant dark tea. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Recommanded Product: 4433-40-3

The Article related to eurotium instant dark tea liquid state fermentation metabolomics, dpph radical scavenging, fermented instant tea, fungal fermentation, metabolome, single fungal culture, α-glucosidase inhibition and other aspects.Recommanded Product: 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Semenov, Vyacheslav E.; Zueva, Irina V.; Mukhamedyarov, Marat A.; Lushchekina, Sofya V.; Kharlamova, Alexandra D.; Petukhova, Elena O.; Mikhailov, Anatoly S.; Podyachev, Sergey N.; Saifina, Lilya F.; Petrov, Konstantin A.; Minnekhanova, Oksana A.; Zobov, Vladimir V.; Nikolsky, Evgeny E.; Masson, Patrick; Reznik, Vladimir S. published an article in 2015, the title of the article was 6-Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease.Application of 626-48-2 And the article contains the following content:

Novel 6-methyluracil derivatives with ω-(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron-withdrawing substituents on the benzyl rings. The compounds are mixed-type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10,000-fold higher than that for human butyrylcholinesterase (hBuChE). Mol. modeling studies indicate that these compounds are bifunctional AChE inhibitors, spanning the enzyme active site gorge and binding to its peripheral anionic site (PAS). In vivo experiments show that the 6-methyluracil derivatives are able to penetrate the blood-brain barrier (BBB), inhibiting brain-tissue AChE. The most potent AChE inhibitor, (1,3-bis[5-(o-nitrobenzylethylamino)pentyl]-6-methyluracil), was found to improve working memory in scopolamine and transgenic APP/PS1 murine models of Alzheimer’s disease, and to significantly decrease the number and area of β-amyloid peptide plaques in the brain. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Application of 626-48-2

The Article related to methyluracil derivative preparation acetylcholinesterase inhibitor alzheimer disease treatment, 6-methyluracil, alzheimer’s disease, acetylcholinesterase, molecular modeling, reversible inhibitors and other aspects.Application of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On December 31, 2016, Modrzejewska, Martyna; Gawronski, Maciej; Skonieczna, Magdalena; Zarakowska, Ewelina; Starczak, Marta; Foksinski, Marek; Rzeszowska-Wolny, Joanna; Gackowski, Daniel; Olinski, Ryszard published an article.Product Details of 4433-40-3 The title of the article was Vitamin C enhances substantially formation of 5-hydroxymethyluracil in cellular DNA. And the article contained the following:

The most plausible mechanism behind active demethylation of 5-methylcytosine involves TET proteins which participate in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine; the latter is further oxidized to 5-formylcytosine and 5-carboxycytosine. 5-Hydroxymethyluracil can be also generated from thymine in a TET-catalyzed process. Ascorbate was previously demonstrated to enhance generation of 5-hydroxymethylcytosine in cultured cells. The aim of this study was to determine the levels of the above-mentioned TET-mediated oxidation products of 5-methylcytosine and thymine after addition of ascorbate, using an isotope-dilution automated online two-dimensional ultra-performance liquid chromatog. with electrospray ionization tandem mass spectrometry. Intracellular concentration of ascorbate was determined by means of ultra-performance liquid chromatog. with UV detection. Irresp. of its concentration in culture medium (10-100 μM) and inside the cell, ascorbate stimulated a moderate (2- to 3-fold) albeit persistent (up to 96-h) increase in the level of 5-hydroxymethylcytosine. However, exposure of cells to higher concentrations of ascorbate (100 μM or 1 mM) stimulated a substantial increase in 5-formylcytosine and 5-carboxycytosine levels. Moreover, for the first time we demonstrated a spectacular (up to 18.5-fold) increase in 5-hydroxymethyluracil content what, in turn, suggests that TET enzymes contributed to the presence of the modification in cellular DNA. These findings suggest that physiol. concentrations of ascorbate in human serum (10-100 μM) are sufficient to maintain a stable level of 5-hydroxymethylcytosine in cellular DNA. However, markedly higher concentrations of ascorbate (ca. 100 μM in the cell milieu or ca. 1 mM inside the cell) were needed to obtain a sustained increase in 5-formylcytosine, 5-carboxycytosine and 5-hydroxymethyluracil levels. Such feedback to elevated concentrations of ascorbate may reflect adaptation of the cell to environmental conditions. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Product Details of 4433-40-3

The Article related to vitamin c dna hydroxymethyluracil formylcytosine carboxycytosine hydroxymethyluracil, 5-carboxycytosine, 5-formylcytosine, 5-hydroxymethylcytosine, 5-hydroxymethyluracil, 5-methylcytosine, ascorbate and other aspects.Product Details of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia