Month: November 2022

On January 21, 2021, Kanouni, Toufike; Arnold, Lee D.; Kaldor, Stephen W.; Murphy, Eric A.; Tyhonas, John published a patent.Reference of 2,5-Dichloro-4-(trifluoromethyl)pyrimidine The title of the patent was Preparation of 4-(pyrrolidin-1-yl)quinazoline, 4-(pyrrolidin-1-yl)isoquinoline, and 1-(pyrrolidin-1-yl)phthalazine derivatives as inhibitors of cyclin-dependent kinases. And the patent contained the following:

The title compounds represented by formula I [ring A = (un)substituted heteroaryl selected from pyridine, pyrazine, pyrimidine, quinoline, isoquinoline, quinazoline, pyrazolopyridine, pyrazolopyrimidine, thienopyrimidine, thienopyridine, pyridopyridine, pyridopyrimidine, or triazene; W = selected from a group having the structure Q-Q13; t = 1 or 2; u = 0, 1, or 2; R1, R2, R3 = each independently H or each (un)substituted C1-4 alkyl, or heterocyclyl(alkyl); R4 = H or (un)substituted C1-4 alkyl, or optionally, if R3 = (un)substituted C1-4 and R4 = (un)substituted, then R3 and R4 together join to form a ring; R5, R6 = each independently H, cyano,NH2, halo, or each (un)substituted C1-4 alkyl, C1-4 alkoxy, or C1-4 aminoalkyl; X = N or CH; Y = N, or C-L1-R11; Z = N or C-L2-R7; L1, L2 = each independently a bond, O, or N(R8); R7 = cyano, halo, or each (un)substituted C1-4 alkyl, C3-7 carbocyclyl, carbocyclyl(alkyl), heterocyclyl, heterocyclyl(alkyl); R8, R9, R10 = each independently H or (un)substituted C1-4 alkyl; R11 = H, cyano, halo, NH2, or each (un)substituted C1-4 alkyl, C3-7 carbocyclyl, carbocyclyl(alkyl), heterocyclyl, or heterocyclyl(alkyl)] or pharmaceutically acceptable salts or solvates thereof are prepared The compounds I are inhibitors of cyclin-dependent kinases (CDKs) and are useful for the treatment of cancer, neoplastic disease, or hyperproliferative disorder in human or animal. Thus, tert-Bu (R)-[1-(7-acrylamidoquinazolin-4-yl)pyrrolidin-3-yl]carbamate was stirred with CF3CO2H in CH2Cl2 at room temperature for 3 h to give (R)-N-[4-(3-aminopyrrolidin-1-yl)quinazolin-7-yl]acrylamide trifluoroacetate which was heated with 2-chloro-5-(trifluoromethyl)pyrimidine in the presence of diisopropylethylamine in DMSO at 80° for 30 min under nitrogen and microwave irradiation to give (R)-N-[4-[3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]pyrrolidin-1-yl]quinazolin-7-yl]acrylamide (II). II showed IC50 of ≤0.10μM against human recombinant CDK12. The experimental process involved the reaction of 2,5-Dichloro-4-(trifluoromethyl)pyrimidine(cas: 785777-98-2).Reference of 2,5-Dichloro-4-(trifluoromethyl)pyrimidine

The Article related to pyrrolidinylquinazoline pyrrolidinylisoquinoline pyrrolidinylphthalazine preparation inhibitor cyclin dependent kinase, cancer neoplastic disease hyperproliferative disorder treatment and other aspects.Reference of 2,5-Dichloro-4-(trifluoromethyl)pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On June 5, 2021, Aybastier, Onder; Demir, Cevdet published an article.HPLC of Formula: 4433-40-3 The title of the article was Optimization and validation of ultrasensitive GC-MS/MS method to measure oxidatively induced DNA damage products and role of antioxidants in oxidation mechanism. And the article contained the following:

Oxidation of DNA due to exposure to reactive oxygen species (ROS) is a major source of DNA damage. ROS induced damage to DNA plays an important role in some diseases such as various cancers, aging and neurodegenerative diseases. The detection of DNA oxidation products plays a major role in assessing the mutagenicity potential of specific exposure. The GC-MS/MS method was developed for the ultrasensitive determination of individual DNA damage products. The validation results revealed that the proposed method was reliable and sensitive. Multiple response surface methodol. (MRSM) was used to optimize derivatization conditions of oxidatively DNA base damage products before GC-MS/MS anal. The optimum derivatization conditions were determined as 40 min for derivatization time, 120°C for derivatization temperature and 1.4 for BSTFA/pyridine ratio under nitrogen atm. The effects of thymol, carvacrol and thymoquinone as antioxidants were investigated on oxidative DNA damage. The determination of the oxidatively induced DNA damage products was performed after adding DNA and antioxidants with different concentrations under oxidative stress. Eighteen DNA base damage products were analyzed simultaneously using GC-MS/MS. This study showed a significant decrease in the amount of DNA base damage products when the antioxidants were present in the medium. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).HPLC of Formula: 4433-40-3

The Article related to dna damage derivatization multiple response surface methodol oxidative stress, dna damage, derivatization, gc–ms/ms, multiple response surface methodology, oxidative stress, validation and other aspects.HPLC of Formula: 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Akbarzadeh, Marzieh; Bakavoli, Mehdi; Eshghi, Hossein; Shiri, Ali; Azizollahi, Hamid; Mague, Joel T. published an article in 2018, the title of the article was Synthesis of 2-substituted-4-methyl-5,13-dihydropyrimido[4′,5′:5,6][1,4]thiazepino[2,3-b]quinoxaline as a new heterocyclic system.Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione And the article contains the following content:

2-Substituted-4-methyl-5,13-dihydropyrimido[4′,5′:5,6][1,4]thiazepino[2,3-b]quinoxalines, e.g., I, were synthesized through cyclocondensation of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine with 3-aminoquinoxaline-2-thiol and subsequent substitution by various secondary amines. Regioselective heterocyclization was confirmed by X-ray crystallog. anal. for 4-methyl-2-(pyrrolidin-1-yl)-5,13-dihydropyrimido[4′,5′:5,6][1,4]thiazepino[2,3-b]quinoxaline (I). The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to chloropyrimidinylmethylthio quinoxalinamine heterocyclization, chloropyrimidothiazepinoquinoxaline preparation secondary amine amination, aminopyrimidothiazepinequinoxaline preparation and other aspects.Quality Control of 6-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On June 30, 2020, Fujimoto, Yoshiaki; Nakanishi, Ryota; Nukatsuka, Mamoru; Matsuoka, Kazuaki; Ando, Koji; Wakasa, Takeshi; Kitao, Hiroyuki; Oki, Eiji; Maehara, Yoshihiko; Mori, Masaki published an article.Electric Literature of 65-71-4 The title of the article was Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil. And the article contained the following:

Trifluridine (FTD) is the active component of the nucleoside chemotherapeutic drug trifluridine/tipiracil (FTD/TPI), which is approved worldwide for the treatment of patients with metastatic gastrointestinal cancer. FTD exerts cytotoxic effects via its incorporation into DNA, but FTD has not been detected in the tumor specimens of patients. The purpose of this study was to detect FTD in tumors resected from metastatic colorectal cancer (mCRC) patients who were administered FTD/TPI. Another purpose was to investigate the turnover rate of FTD in tumors and bone marrow in a mouse model. Tumors and normal tissue specimens were obtained from mCRC patients who were administered FTD/TPI or placebo at Kyushu University Hospital. Tumors and bone marrow were resected from mice with peritoneal dissemination treated with FTD/TPI. To detect and quantitate FTD incorporated into DNA, immunohistochem. staining of paraffin-embedded specimens (IHC-p staining) and slot-blot anal. of DNA purified from these tissues were performed using an anti-BrdU antibody. IHC-p staining of proliferation and apoptosis markers was also performed. FTD was detected in metastatic tumors obtained from mCRC patients who were administered FTD/TPI, but who had discontinued the treatment several weeks before surgery. In a peritoneal dissemination mouse model, FTD was still detected in tumors 13 days after the cessation of FTD/TPI treatment, but had disappeared from bone marrow within 6 days. These results indicate that FTD persists longer in tumors than in bone marrow, which may cause a sustained antitumor effect with tolerable hematotoxicity. 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 metastatic colorectal cancer human, anti-brdu antibody, liver metastasis, peritoneal dissemination, tas-102), trifluridine (ftd), trifluridine/tipiracil (ftd/tpi and other aspects.Electric Literature of 65-71-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On June 30, 2021, Kuramochi, Hidekazu; Yamada, Takeshi; Yoshida, Yoichiro; Matsuda, Akihisa; Kamiyama, Hirohiko; Kosugi, Chihiro; Ishibashi, Keiichiro; Fukazawa, Atsuko; Ihara, Keisuke; Sonoda, Hiromichi; Yoshimatsu, Kazuhiko; Yoshida, Hiroshi; Hasegawa, Suguru; Sakamoto, Kazuhiro; Ishida, Hideyuki; Koda, Keiji; TAS CC3 Study Group published an article.Safety of 5-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was The pre-treatment lymphocyte-to-monocyte ratio predicts efficacy in metastatic colorectal cancer treated with TAS-102 and bevacizumab. And the article contained the following:

Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3rd-line treatment. We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc anal. Receiver operating characteristic curve analyses of the 3 inflammation-based scores vs. DC showed the best predictive performance for LMR, followed by NLR and PLR. The high-LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%). The high-LMR group showed significantly longer survival than the low group (4.9 vs. 2.3 m for median PFS) (21.0 vs. 6.1 m for median OS). The pre-treatment LMR is a valid predictive and prognostic biomarker for mCRC patients undergoing TAS-102 and bevacizumab treatment. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Safety of 5-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to tas102 bevacizumab lymphocyte monocyte inflammation colorectal cancer, tas-102, bevacizumab, colorectal cancer, lymphocyte-to-monocyte ratio (lmr), neutrophil-to-lymphocyte ratio (nlr) and other aspects.Safety of 5-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On June 11, 2007, Harbottle, Gareth W.; Feeder, Neil; Gibson, Karl R.; Glossop, Mel; Maw, Graham N.; Million, William A.; Morel, Florence F.; Osborne, Simon; Poinsard, Cedric published an article.Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine The title of the article was Microwave-assisted synthesis of mGluR1 ligands: carbon, nitrogen, and oxygen linked derivatives of pyrido[3,4-d]pyrimidin-4-ylamines. And the article contained the following:

The syntheses of 6-fluoropyrido[3,4-d]pyrimidin-4-ylamine derivatives is reported herein. Methods for generating C-, N-, and O-linked analogs by subsequent nucleophilic aromatic substitution of fluoride with alcs. or amines under microwave irradiation are described. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

The Article related to pyridopyrimidinylamine mglur1 ligand preparation, fluoropyridopyrimidinylamine amine nucleophilic aromatic substitution, alc fluoropyridopyrimidinylamine nucleophilic aromatic substitution and other aspects.Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

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

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

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 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