Category: 3764-01-0

In 2017,Li, Wenlu; Sun, Qinsheng; Song, Lu; Gao, Chunmei; Liu, Feng; Chen, Yuzong; Jiang, Yuyang published 《Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings》.European Journal of Medicinal Chemistry published the findings.Name: 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of mols. simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-neg. breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Fairhurst, Robin A.; Furet, Pascal; Imbach-Weese, Patricia; Stauffer, Frederic; Rueeger, Heinrich; McCarthy, Clive; Ripoche, Sebastien; Oswald, Susanne; Arnaud, Bertrand; Jary, Aline; Maira, Michel; Schnell, Christian; Guthy, Daniel A.; Wartmann, Markus; Kiffe, Michael; Desrayaud, Sandrine; Blasco, Francesca; Widmer, Toni; Seiler, Frank; Gutmann, Sascha; Knapp, Mark; Caravatti, Giorgio published an article in Journal of Medicinal Chemistry. The title of the article was 《Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor》.Quality Control of 2,4,6-Trichloropyrimidine The author mentioned the following in the article:

Balanced pan-class I phosphoinositide 3-kinase inhibition as an approach to cancer treatment offers the prospect of treating a broad range of tumor types and/or a way to achieve greater efficacy with a single inhibitor. Taking buparlisib as the starting point, the balanced pan-class I PI3K inhibitor 40 (NVP-CLR457) was identified with what was considered to be a best-in-class profile. Key to the optimization to achieve this profile was eliminating a microtubule stabilizing off-target activity, balancing the pan-class I PI3K inhibition profile, minimizing CNS penetration, and developing an amorphous solid dispersion formulation. A rationale for the poor tolerability profile of 40 in a clin. study is discussed. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Taylor, Connor J.; Seki, Hikaru; Dannheim, Friederike M.; Willis, Mark J.; Clemens, Graeme; Taylor, Brian A.; Chamberlain, Thomas W.; Bourne, Richard A. published their research in Reaction Chemistry & Engineering in 2021. The article was titled 《An automated computational approach to kinetic model discrimination and parameter estimation》.Application of 3764-01-0 The article contains the following contents:

We herein report exptl. applications of a novel, automated computational approach to chem. reaction network (CRN) identification. This report shows the first chem. applications of an autonomous tool to identify the kinetic model and parameters of a process, when considering both catalytic species and various integer and non-integer orders in the model′s rate laws. This kinetic anal. methodol. requires only the input of the species within the chem. system (starting materials, intermediates, products, etc.) and corresponding time-series concentration data to determine the kinetic information of the chem. of interest. This is performed with minimal human interaction and several case studies were performed to show the wide scope and applicability of this process development tool. The approach described herein can be employed using exptl. data from any source and the code for this methodol. is also provided open-source. In the experimental materials used by the author, we found 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Van de Poel, Amanda; Toledo-Sherman, Leticia; Breccia, Perla; Cachope, Roger; Bate, Jennifer R.; Angulo-Herrera, Ivan; Wishart, Grant; Matthews, Kim L.; Martin, Sarah L.; Peacock, Marcus; Barnard, Amy; Cox, Helen C.; Jones, Graham; McAllister, George; Vater, Huw; Esmieu, William; Clissold, Cole; Lamers, Marieke; Leonard, Philip; Jarvis, Rebecca E.; Blackaby, Wesley; Eznarriaga, Maria; Lazari, Ovadia; Yates, Dawn; Rose, Mark; Jang, Sung-Wook; Munoz-Sanjuan, Ignacio; Dominguez, Celia published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Structure-Based Exploration of Selectivity for ATM Inhibitors in Huntington’s Disease》.Safety of 2,4,6-Trichloropyrimidine The article contains the following contents:

Our group has recently shown that brain-penetrant ataxia telangiectasia-mutated (ATM) kinase inhibitors may have potential as novel therapeutics for the treatment of Huntington’s disease (HD). However, the previously described pyranone-thioxanthenes (e.g., 4) failed to afford selectivity over a vacuolar protein sorting 34 (Vps34) kinase, an important kinase involved with autophagy. Given that impaired autophagy has been proposed as a pathogenic mechanism of neurodegenerative diseases such as HD, achieving selectivity over Vps34 became an important objective for our program. Here, we report the successful selectivity optimization of ATM over Vps34 by using X-ray crystal structures of a Vps34-ATM protein chimera where the Vps34 ATP-binding site was mutated to approx. that of an ATM kinase. The morpholino-pyridone and morpholino-pyrimidinone series that resulted as a consequence of this selectivity optimization process have high ATM potency and good oral bioavailability and have lower mol. weight, reduced lipophilicity, higher aqueous solubility, and greater synthetic tractability compared to the pyranone-thioxanthenes. In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Safety of 2,4,6-Trichloropyrimidine) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Safety of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《General dual functionalisation of biomacromolecules via a cysteine bridging strategy》 was written by Walsh, Stephen J.; Iegre, Jessica; Seki, Hikaru; Bargh, Jonathan D.; Sore, Hannah F.; Parker, Jeremy S.; Carroll, Jason S.; Spring, David R.. COA of Formula: C4HCl3N2 And the article was included in Organic & Biomolecular Chemistry in 2020. The article conveys some information:

Site-selective modification of peptides and proteins resulted in the development of a host of novel tools for the study of cellular systems or the synthesis of enhanced biotherapeutics. There is a need for useful methodologies that enable site-selective modification of native peptides or proteins, which is even more prevalent when modification of the biomol. with multiple payloads is desired. Herein, the authors report the development of a novel dual functional divinylpyrimidine (dfDVP) platform that enables robust and modular modification of peptides, antibody fragments and antibodies. These biomacromols. could be easily functionalized with a range of functional payloads (e.g. fluorescent dyes, cytotoxic warheads or cell-penetrating tags). Importantly, the dual functionalized peptides and antibodies demonstrated exquisite bioactivity in a range of in vitro cellular assays, showcasing the enhanced utility of these bioactive conjugates. In the experiment, the researchers used many compounds, for example, 2,4,6-Trichloropyrimidine(cas: 3764-01-0COA of Formula: C4HCl3N2)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.COA of Formula: C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration》 were Cao, Hengyi; Zhu, Guangya; Sun, Lin; Chen, Ge; Ma, Xinxin; Luo, Xiao; Zhu, Jidong. And the article was published in European Journal of Medicinal Chemistry in 2019. Application of 3764-01-0 The author mentioned the following in the article:

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5, (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(7-(trifluoromethyl)4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one [2379528-08-0], exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclin. candidate to treat IDH1-mutant brain tumors. In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Synthesis and biological evaluation of aurora kinases inhibitors based on N-trisubstituted pyrimidine scaffold》 was written by Long, Liang; Luo, Yu; Hou, Zhi-Jie; Ma, Hua-Juan; Long, Zi-Jie; Tu, Zheng-Chao; Huang, Lin-Jie; Liu, Quentin; Lu, Gui. Formula: C4HCl3N2This research focused ontrisubstituted pyrimidine preparation aurora kinase inhibitor antitumor human SAR; Anticancer drug; Aurora kinase inhibitor; Leukemia; N-trisubstituted pyrimidines; Synthesis. The article conveys some information:

The inhibition of the members of aurora kinase family using ATP-competitive small mols. was an effective method for anticancer therapeutics. Based on this concept, synthesis of new N-trisubstituted pyrimidine derivatives I [Ar = 4-FC6H4, 3-F-4-CO2MeC6H3, 3,4,5-MeO3C6H2, etc.] and evaluation of their biol. activities and stabilities were done. Among them, compound I [Ar = 3-Cl-4-FC6H3] showed the best inhibition against aurora A kinase (IC50 = 7.1 nM), human leukemia cell line U937 (IC50 = 12.2 nM) and the growth of U937 xenograft tumors in vivo. By flow cytometry and immunofluorescence anal. of U937, it was found that compound I [Ar = 3-Cl-4-FC6H3] could induced polyploidy formation including (4N, 8N and 16N) and induced defects in both chromosome alignment and spindle formation. Furthermore, compound I [Ar = 3-Cl-4-FC6H3] exhibited good chem., phys., and thermal stabilities. All these results suggested that compound I [Ar = 3-Cl-4-FC6H3] was a promising lead compound for further development of anticancer drugs.2,4,6-Trichloropyrimidine(cas: 3764-01-0Formula: C4HCl3N2) was used in this study.

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Formula: C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of uracil-bearing DAPYs derivatives as novel HIV-1 NNRTIs via crystallographic overlay-based molecular hybridization》 was written by Zhang, Heng; Tian, Ye; Kang, Dongwei; Huo, Zhipeng; Zhou, Zhongxia; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong. Category: pyrimidinesThis research focused onuracil containing diarylpyrimidine preparation anti HIV QSAR; DAPYs; Drug design; Molecular hybridization; NNRTIs; Physicochemical properties; Uracil. The article conveys some information:

A novel series of uracil-bearing DAPYs derivatives were designed and synthesized via structure-based mol. hybridization to discover compounds with improved anti-resistance profiles. Anti-HIV activity of the designed compounds was tested in MT-4 cell cultures. The most promising compound I showed excellent activity with EC50 value of 5.6 nM against wide-type HIV-1 and low cytotoxicity (SI > 50000). Activity against the clinic prevalent mutant strains was also tested, suggesting that I was sensitive to E138K (EC50 = 34.2 nM). Primary drug-like properties, such as water solubility and logP, were evaluated by experiment or calculation, which indicated that introducing an uracil can improve solubility The mol. modeling accompanied with the preliminary SAR correlations paved the way for the next round of rational design of potent anti-HIV agents. The experimental part of the paper was very detailed, including the reaction process of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Category: pyrimidines)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Name: 2,4,6-TrichloropyrimidineIn 2016 ,《Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Hu, Jianping; Wang, Xin; Chen, Lin; Huang, Min; Tang, Wei; Zuo, Jianping; Liu, Yu-Chih; Shi, Zhe; Liu, Rongfeng; Shen, Jingkang; Xiong, Bing. The article conveys some information:

The histone methylation on lysine residues is one of the most studied posttranslational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure-activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, the authors initialized a medicinal chem. modification based on the GSK-J1 structure. Finally, the authors found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The Et ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-α production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies》 was published in Archiv der Pharmazie (Weinheim, Germany) in 2020. These research results belong to Qin, Qiaohua; Wu, Tianxiao; Yin, Wenbo; Sun, Yixiang; Zhang, Xiangyu; Wang, Ruifeng; Guo, Jing; Zhao, Dongmei; Cheng, Maosheng. Synthetic Route of C4HCl3N2 The article mentions the following:

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biol. activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC50 = 18.4, 5.9, and 20.4 nM, resp.). From the cellular assay, compound B6 exhibited the highest potency with an IC50 value of 2.533μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and mol. docking studies against PAK4. The detailed structure-activity relationship based on the biochem. activities and mol. docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: -7.593 kcal/mol). The mol. docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor. In the experiment, the researchers used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Synthetic Route of C4HCl3N2)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Synthetic Route of C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia