Category: 626-48-2

Qureshi, Wasay Mohiuddin Shaikh; Pratten, Margaret K. published an article in 2018, the title of the article was Chick embryonic cardiomyocyte micromass system for assessing developmental cardiotoxicity of drugs.Product Details of 626-48-2 And the article contains the following content:

Heart is the first mesodermal organ to develop and is sensitive to life-threatening toxic effects of drugs during development. A number of methods have been devised to study developmental cardiotoxic effects of drugs including micromass system. The micromass system involves the culture of primary embryonic cells and reestablishment of tissue system in vitro. In chick embryonic cardiomyocyte micromass system the chick heart cells are cultured in a small volume at a very high cell d. These cells form synchronized contracting foci. Addition of drugs to this system allows us to study the developmental cardiotoxic effects at mol. level. Using appropriate end points and mol. marker or adopting high-throughput screening, this method can further help to identify and avoid the use of cardiotoxic compounds during development. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Product Details of 626-48-2

The Article related to heart cardiomyocyte micromass system developmental cardiotoxicity vpa bpn, cardiomyocytes, chick, connexin43, developmental toxicology, micromass, reactive oxygen species, teratogens and other aspects.Product Details of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On September 18, 2015, Lin, Meng-I.; Su, Bo-Han; Lee, Chia-Hsin; Wang, Suz-Ting; Wu, Wen-Chun; Dangate, Prasad; Wang, Shi-Yun; Huang, Wen-I.; Cheng, Ting-Jen; Lin, Olivia A.; Cheng, Yih-Shyun E.; Tseng, Yufeng Jane; Sun, Chung-Ming published an article.Name: 6-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was Synthesis and inhibitory effects of novel pyrimido-pyrrolo-quinoxalinedione analogues targeting nucleoproteins of influenza A virus H1N1. And the article contained the following:

The influenza nucleoprotein (NP) is a single-strand RNA-binding protein and the core of the influenza ribonucleoprotein (RNP) particle that serves many critical functions for influenza replication. NP has been considered as a promising anti-influenza target. A new class of anti-influenza compounds, nucleozin and analogs were reported recently in several laboratories to inhibit the synthesis of influenza macromols. and prevent the cytoplasmic trafficking of the influenza RNP. In this study, pyrimido-pyrrolo-quinoxalinedione (PPQ) analogs as a new class of novel anti-influenza agents are reported. Compound PPQ-581 was identified as a potential anti-influenza lead with EC50 value of 1 μM for preventing virus-induced cytopathic effects. PPQ produces similar anti-influenza effects as nucleozin does in influenza-infected cells. Treatment with PPQ at the beginning of H1N1 infection inhibited viral protein synthesis, while treatment at later times blocked the RNP nuclear export and the appearance of cytoplasmic RNP aggregation. PPQ resistant H1N1 (WSN) viruses were isolated and found to have a NPS377G mutation. Recombinant WSN carrying the S377G NP is resistant to PPQ in anti-influenza and RNA polymerase assays. The WSN virus with the NPS377G mutation also is devoid of the PPQ-mediated RNP nuclear retention and cytoplasmic aggregation. The NPS377G expressing WSN virus is not resistant to the reported NP inhibitors nucleozin. Similarly, the nucleozin resistant WSN viruses are not resistant to PPQ, suggesting that PPQ targets a different site from the nucleozin-binding site. The results also suggest that NP can be targeted through various binding sites to interrupt the crucial RNP trafficking, resulting in influenza replication inhibition. 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 preparation quinoxalinedione nucleoprotein antiviral influenza virus, anti-influenza, influenza nucleoprotein, pyrimido-pyrrolo-quinoxalinedione (ppq), rna-dependent rna polymerase and other aspects.Name: 6-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Cawrse, Brian M.; Lapidus, Rena S.; Cooper, Brandon; Choi, Eun Yong; Seley-Radtke, Katherine L. published an article in 2018, the title of the article was Anticancer Properties of Halogenated Pyrrolo[3,2-d]pyrimidines with Decreased Toxicity via N5 Substitution.Synthetic Route of 626-48-2 And the article contains the following content:

Halogenated pyrrolo[3,2-d]pyrimidine analogs have shown antiproliferative activity in recent studies, with cell accumulation occurring in the G2/M stage without apoptosis. However, the mechanism of action and pharmacokinetic (PK) profile of these compounds has yet to be determined To investigate the PK profile of these compounds, a series of halogenated pyrrolo[3,2-d]pyrimidine compounds was synthesized and first tested for activity in various cancer cell lines followed by a mouse model. EC50 values ranged from 0.014 to 14.5 μM, and maximum tolerated doses (MTD) in mice were between 5 and 10 mg kg-1. This indicates a wide variance in activity and toxicity that necessitates further study. To decrease toxicity, a second series of compounds was synthesized with N5-alkyl substitutions in an effort to slow the rate of metabolism, which was thought to be leading to the toxicity. The N-substituted compounds demonstrated comparable cell line activity (EC50 values between 0.83-7.3 μM) with significantly decreased toxicity (MTD=40 mg kg-1). Finally, the PK profile of the active N5-substituted compound shows a plasma half-life of 32.7 min, and rapid conversion into the parent unsubstituted analog. Together, these data indicate that halogenated pyrrolo[3,2-d]pyrimidines present a promising lead into potent antiproliferative agents with tunable activity and toxicity, and rapid metabolism 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 antitumor halogenated pyrrolo pyrimidine preparation toxicity pharmacokinetics prodrug, anticancer, antiproliferative, prodrugs, pyrrolopyrimidines, triple-negative breast cancer and other aspects.Synthetic Route of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ramana, M. M. V.; Pawar, Sanjay C. published an article in 2015, the title of the article was A novel and expedient synthesis of 1,3-dialkyl-6-methylpyrimidinediones.Application of 626-48-2 And the article contains the following content:

A series of 1,3-dialkyl-6-methylpyrimidinediones I [R = Me, Et, n-Pr, i-Pr, n-Bu, s-Bu] was synthesized via double Chapman rearrangement of 2,4-dialkoxy-6-methylpyrimidines under conventional heating as well as microwave irradiation 2,4-Dialkoxy-6-methylpyrimidines were prepared by condensation of 2,4-dichloro-6-methylpyrimidine with various alcs. Microwave-assisted method with the advantages of reduced reaction times and better reaction yields, provided a simpler and environmentally friendly alternative for conventional procedures. 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 dialkyl pyrimidinedione preparation green chem, dialkoxy pyrimidine preparation double chapman rearrangement microwave irradiation, dichloro pyrimidine aliphatic alc condensation and other aspects.Application of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On October 31, 2022, Ma, Siqi; Cong, Zhaoqing; Wei, Jiaxing; Chen, Weiya; Ge, Di; Yang, Feifei; Liao, Yonghong published an article.Recommanded Product: 6-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was Pulmonary delivery of size-transformable nanoparticles improves tumor accumulation and penetration for chemo-sonodynamic combination therapy. And the article contained the following:

Very little is currently known about how inhaled nanomedicine for lung cancer treatment overcomes biol. barriers hampering the tumor availability of drug and nanoparticles. Here, we developed a size-transformable nanocarrier (∼ 119 nm) in which small-size nanoparticles (∼ 28 nm) were loaded in the large nanocarrier after the addition of modified hyaluronan and could be released upon size-transformation at tumor tissue. Subsequently, the pulmonary and tumor pharmacokinetics of the two nanocarriers containing 7-ethyl-10-hydroxycamptothecin (SN38) and a covalently linked fluorescent sonosensitizer were comparatively investigated after intratracheal instillation to mice bearing orthotopic Lewis lung carcinoma tumors. The results showed that both instilled nanoparticles seemed to transport drug to tumor by direct access and transcytosis of nanoparticles, and diffusion of the released drug with the latter accounting for a great proportion of the drug tumor bioavailability. Relative to the small-size nanocarrier, the size-transformable counterpart appeared to restrict the mucociliary and absorption clearances from the lung and the clearance from the tumor interstitium to circulation, leading to increases in lung and tumor bioavailability of SN38 by 58.5% and 199%, resp. In addition, the size-transformable nanoformulation conferred deep tumor penetration and sustained levels of both sonosensitizer and SN38 within tumors and simultaneously exerted sonodynamic- and chemo-therapies. Overall, the pulmonary delivery of size-transformable nanocarrier could co-deliver sonosensitizer and drug to deep tumor sites with enhanced tumor accumulation to realize combination therapy in lung cancer. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Recommanded Product: 6-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to sn38 nanoparticle drug delivery sonodynamic therapy lewis lung carcinoma, inhaled nanomedicine, lung cancer, size-transformation, tumor penetration, tumor pharmacokinetics and other aspects.Recommanded Product: 6-Methylpyrimidine-2,4(1H,3H)-dione

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

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 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

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 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