Day: October 21, 2022

Category: pyrimidinesIn 2022 ,《Synthesis and biological evaluation of 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives as novel dual FLT3/CDK4 inhibitors》 appeared in Bioorganic Chemistry. The author of the article were Li, Xiandeng; Yang, Tao; Hu, Mengshi; Yang, Yingxue; Tang, Minghai; Deng, Dexin; Liu, Kongjun; Fu, Suhong; Tan, Yan; Wang, Huan; Chen, Yong; Zhang, Chufeng; Guo, Yong; Peng, Bin; Si, Wenting; Yang, Zhuang; Chen, Lijuan. The article conveys some information:

Herein, based on the previously reported JAK2/FLT3 inhibitor, the synthesis, structure-activity relationship and biol. evaluation of a series of unique 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives, e.g., I, was described that inhibited FLT3 and CDK4 kinases. The optimized compound exhibited low nanomolar range activities with IC50 values of 11 and 7 nM for FLT3 and CDK4, resp. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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

In 2018,Feng, Da; Wei, Fenju; Wang, Zhao; Kang, Dongwei; Zhan, Peng; Liu, Xinyong published 《Development of a practical synthesis of etravirine via a microwave-promoted amination》.Chemistry Central Journal published the findings.Synthetic Route of C4HCl3N2 The information in the text is summarized as follows:

Etravirine (ETV) was approved as the second generation drug for use in individuals infected with HIV-1 in 2008 by the U.S. FDA with its unique antiviral activity, high specificity, and low toxicity. However, there are some shortcomings of the existing synthetic routes, such as the long reaction time and poor yield. This article describes our efforts to develop an efficient, practical, microwave-promoted synthetic method for one key intermediate of ETV, which is capable of being operated on a scale-up synthesis level. Through this optimized synthetic procedure, the amination reaction time decreased from 12 h to 15 min and the overall yield improved from 30.4 to 38.5%. Overall, we developed a practical synthesis of ETV via a microwave-promoted method, and the synthetic procedure could be amenable to scale-up, and production costs could be significantly lowered. 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

《6-(Ar)Alkylamino-Substituted Uracil Derivatives: Lipid Mimetics with Potent Activity at the Orphan G Protein-Coupled Receptor 84 (GPR84)》 was written by Pillaiyar, Thanigaimalai; Koese, Meryem; Namasivayam, Vigneshwaran; Sylvester, Katharina; Borges, Gleice; Thimm, Dominik; von Kuegelgen, Ivar; Mueller, Christa E.. Synthetic Route of C4HCl3N2This research focused onuracil amino substituted preparation GPR84 agonistic activity. The article conveys some information:

GPR84, a Gi protein-coupled receptor that is activated by medium-chain (hydroxy)fatty acids, appears to play an important role in inflammation, immunity, and cancer. Recently, 6-octylaminouracil has been reported to act as an agonist at GPR84. Here, we describe the synthesis of 69 derivatives and analogs which represent new compounds They were evaluated in (a) cyclic adenosine monophosphate accumulation and (b) β-arrestin assays in human GPR84-expressing cells. Potent nonbiased as well as G protein-biased agonists were developed, e.g., 6-hexylamino-2,4(1H,3H)-pyrimidinedione (PSB-1584, EC50 5.0 nM (a), 3.2 nM (b), bias factor: 0) and 6-((p-chloro- and p-bromo-phenylethyl)amino)-2,4(1H,3H)-pyrimidinedione (PSB-16434, EC50 7.1 nM (a), 520 nM (b), bias factor: 1.9 = 79-fold Gi pathway-selective; I, PSB-17365, EC50 2.5 nM (a), 100 nM (b), bias factor 1.3 = 20-fold selective), which were selective vs. other free fatty acid-activated receptors. Compounds II and I were found to be metabolically stable upon incubation with human liver microsomes. A pharmacophore model was created on the basis of structurally diverse lipidlike GPR84 agonists. After reading the article, we found that the author 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 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.Synthetic Route of C4HCl3N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

HPLC of Formula: 771-81-3On November 24, 1998 ,《The C-Terminal Region of the Stalk Domain of Ubiquitous Human Kinesin Heavy Chain Contains the Binding Site for Kinesin Light Chain》 appeared in Biochemistry. The author of the article were Diefenbach, Russell J.; Mackay, Joel P.; Armati, Patricia J.; Cunningham, Anthony L.. The article conveys some information:

The motor protein kinesin is a heterotetramer composed of two heavy chains of ∼120 kDa and two light chains of ∼65 kDa protein. Kinesin motor activity is dependent on the presence of ATP and microtubules. The kinesin light chain-binding site in human kinesin heavy chain was determined by reconstituting in vitro a complex of recombinant heavy and light chains. The proteins expressed in bacteria included oligohistidine-tagged fragments of human ubiquitous kinesin heavy chain, spanning most of the stalk and all of the tail domain (amino acids 555-963); and untagged, essentially full-length human kinesin light chain (4-569) along with N-terminal (4-363) and C-terminal (364-569) light chain fragments. Heavy chain fragments were attached to Ni2+-charged beads and incubated with untagged light chain fragments. Anal. of eluted complexes by SDS-PAGE and immunoblotting mapped the light chain-binding site in heavy chain to amino acids 771-813, a region close to the C-terminal end of the heavy chain stalk domain. In addition, only the full-length and N-terminal kinesin light chain fragments bound to this heavy chain region. Within this heavy chain region are four highly conserved contiguous heptad repeats (775-802) which are predicted to form a tight α-helical coiled-coil interaction with the heptad repeat-containing N-terminus of the light chain, in particular region 106-152 of human light chain. This predicted hydrophobic, α-helical coiled-coil interaction is supported by both CD spectroscopy of the recombinant kinesin heavy chain fragment 771-963, which displays an α-helical content of 70%, and the resistance of the heavy/light chain interaction to high salt (0.5 M). After reading the article, we found that the author used 4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3HPLC of Formula: 771-81-3)

4-Amino-2-(methylthio)pyrimidine-5-carboxylic acid(cas: 771-81-3) belongs to anime. Nitrous acid converts secondary amines (aliphatic or aromatic) to N-nitroso compounds (nitrosamines): R2NH + HNO2 → R2N―NO. Some nitrosamines are potent cancer-inducing substances, and their possible formation is a serious consideration when nitrites, which are salts of nitrous acid, are present in foods or pharmaceutical preparations. Tertiary amines give rise to nitrosamines more slowly; an alkyl group is eliminated as an aldehyde or ketone, along with nitrous oxide, N2O.HPLC of Formula: 771-81-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Moreno-Manas, Marcial; Pleixats, Roser; Villarroya, Merce published an article on February 12 ,1993. The article was titled 《Palladium-catalyzed allylation of pyrimidine-2,4-diones (uracils) and of 6-membered heterocyclic ambident sulfur nucleophiles》, and you may find the article in Tetrahedron.Recommanded Product: 6-Methoxypyrimidine-2,4(1H,3H)-dione The information in the text is summarized as follows:

Pd(0)-catalyzed allylation of six-membered ambident heterocycles (e.g., 2-pyridone, 6-methyl-2-thiouracil, and 2-thiobarbituric acid) bearing NH-CO, NH-CS and CH2-CO moieties obey the regioselectivity rules: C > O; N > O; S > H, NH-CO > NH-CS. Uracil and 5-methyluracil (thymine) do not show regioselectivity (N-1 = N-3) whereas 6-methyluracil is regioselectively allylated at N-3 (N-3 > N-1). In addition to this study using 6-Methoxypyrimidine-2,4(1H,3H)-dione, there are many other studies that have used 6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6Recommanded Product: 6-Methoxypyrimidine-2,4(1H,3H)-dione) was used in this study.

6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Recommanded Product: 6-Methoxypyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Iron(II) complexes with diazinyl-NHC ligands: impact of π-deficiency of the azine core on photophysical properties》 were Darari, Mohamed; Domenichini, Edoardo; Frances-Monerris, Antonio; Cebrian, Cristina; Magra, Kevin; Beley, Marc; Pastore, Mariachiara; Monari, Antonio; Assfeld, Xavier; Haacke, Stefan; Gros, Philippe C.. And the article was published in Dalton Transactions in 2019. Application In Synthesis of 2,4-Dichloropyrimidine The author mentioned the following in the article:

Ligand field enhancing N-heterocyclic carbene (NHC) ligands were recently shown to prevent photo-induced spin crossover in Fe(II) complexes due to their intricate effects on the electronic excited state structure. Due to their pico- to nanosecond lifetimes, these complexes are now good candidates for photo-sensitizing applications. Herein authors report the synthesis and photophys. characterization of a new family of homoleptic Fe(II) complexes with C^N^C ligands involving diazines as the central N-heteroaromatic ligand. For these four carbene bond complexes, ultrafast transient absorption spectroscopy revealed a significant improvement of the excited-state lifetime. A record 32 ps lifetime was measured for a complex bearing a ligand combining a π-deficient pyrazine nucleus and a benzimidazolylidene as NHC. When compared to other azine-based ligands investigated, they argue that the lifetimes are modulated by a small excited state barrier expressing the ability of the ligand to reach the Fe-N distance needed for internal conversion to the ground state. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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 In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Sulfatase-cleavable linkers for antibody-drug conjugates》 was published in Chemical Science in 2020. These research results belong to Bargh, Jonathan D.; Walsh, Stephen J.; Isidro-Llobet, Albert; Omarjee, Soleilmane; Carroll, Jason S.; Spring, David R.. Reference of 2,4,6-Trichloropyrimidine The article mentions the following:

Antibody-drug conjugates (ADCs) are a class of targeted drug delivery agents combining the cell-selectivity of monoclonal antibodies (mAbs) and the cytotoxicity of small mols. These two components are joined by a covalent linker, whose nature is critical to the efficacy and safety of the ADC. Enzyme-cleavable dipeptidic linkers have emerged as a particularly effective ADC linker type due to their ability to selectively release the payload in the lysosomes of target cells. However, these linkers have a number of drawbacks, including instability in rodent plasma and their inherently high hydrophobicity. Here we show that arylsulfate-containing ADC linkers are cleaved by lysosomal sulfatase enzymes to tracelessly release their payload, while circumventing the instability problems associated with dipeptide-linkers. When incorporated with trastuzumab and the highly potent monomethyl auristatin E (MMAE) payload, the arylsulfate-containing ADC 2 and ADC 3 were more cytotoxic than the non-cleavable ADC 4 against HER2-pos. cells, while maintaining selectivity over HER2-neg. cells. We propose that the stability, solubility and synthetic tractability of our arylsulfate linkers make them an attractive new motif for cleavable ADC linkers, with clear benefits over the widely used dipeptidic linkers. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Reference of 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.Reference of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Synthesis and biological evaluation of 6-phenylpurine linked hydroxamates as novel histone deacetylase inhibitors》 was written by Chen, Dizhong; Soh, Chang Kai; Goh, Wei Huang; Wang, Zilong; Wang, Haishan. Product Details of 90213-66-4 And the article was included in Bioorganic Chemistry in 2020. The article conveys some information:

A series of 6-phenylpurine based hydroxamates I (R = morpholin-4-yl, diethylaminyl, dimethylaminyl, pyrrolidin-1-yl; R1 = Et, iso-Pr, Pr, cyclopentyl, pentan-3-yl; R2 = 3-[(hydroxycarbamoyl)methyl]oxidanyl, 4-[4-(hydroxycarbamoyl)butoxy]methyl, 3-[4-(hydroxycarbamoyl)piperidin-1-yl]methyl, etc.) have been designed, synthesized and evaluated. Compound I (R = morpholin-4-yl; R1 = isopropyl; R2 = 3-[3-(hydroxycarbamoyl)propyl]oxidanyl (A)) and its analogs are potent histone deacetylase (HDAC) but weak PI3K/mTOR inhibitors. These compounds demonstrated broad anti-cancer activities against 38 cancer cell lines with leukemia, lymphoma, and the majority of liver cancer cell lines exhibiting the most sensitivity towards these compounds Compound (A) demonstrated modulation of HDAC targets in vitro in a dose-dependent manner. It has good in vitro ADME profile that translated into a greatly improved pharmacokinetic profile., the compound (A) also demonstrated modulation of HDACs in tumors in a PC-3 xenograft model. It was further evaluated in combination therapies in vitro. It exhibited additive or synergistic growth inhibition effect in HepG2 cells when combined with a number of approved drugs such as sorafenib, sunitinib, and erlotinib. Hence, compound (A) has the potential to be combined with the above to treat advanced liver cancer. As such, current data warrant further evaluation, optimization, and subsequent in vivo validation of the potential combination therapies. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Product Details of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bouffard, Elise; Zaro, Balyn W.; Dix, Melissa M.; Cravatt, Benjamin; Wong, Chi-Huey published their research in Tetrahedron Letters in 2021. The article was titled 《Refinement of covalent EGFR inhibitor AZD9291 to eliminate off-target activity》.Recommanded Product: 2,4-Dichloropyrimidine The article contains the following contents:

Non-small-cell lung cancer (NSCLC) is a major disease that accounts for 85% of all lung cancer cases which claimed around 1.8 billion lives worldwide in 2020. Tyrosine kinase inhibitors (TKIs) that target EGFR have been used for the treatment of NSCLC, but often develop drug resistance, and the covalent inhibitor AZD9291 (I) has been developed to tackle the problem of drug resistance mediated by the T790M EGFR mutation; however, there is a side effect of hyperglycemia that may be due to off-target activity. This study examines analogs of AZD9291 by chem. proteomics, identifying analogs that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Recommanded Product: 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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.Recommanded Product: 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reference of 2,4-DichloropyrimidineIn 2021 ,《Structure activity relationships and the binding mode of quinolinone-pyrimidine hybrids as reversal agents of multidrug resistance mediated by P-gp》 appeared in Scientific Reports. The author of the article were Laiolo, Jeronimo; Lanza, Priscila Ailin; Parravicini, Oscar; Barbieri, Cecilia; Insuasty, Daniel; Cobo, Justo; Vera, D. Mariano Adolfo; Enriz, Ricardo Daniel; Carpinella, Maria Cecilia. The article conveys some information:

P-gp-associated multidrug resistance is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure-activity relationships showed that the number of methoxy groups, an optimal length of the mol. in its extended conformation, and at least one flexible methylene group bridging the quinolinone to the moiety bearing the pyrimidine favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent exptl. structure of P-gp co-crystallized with paclitaxel. Anal. of the mol. interactions stabilizing the different mol. complexes determined by MD and QTAIM showed that binding to key residues from TMH 4-7 and 12 is required for inhibition. After reading the article, we found that the author used 2,4-Dichloropyrimidine(cas: 3934-20-1Reference of 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) 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.Reference of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia