Tag: 100-200

《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

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

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

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

《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

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

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 2022,Wang, Xinran; Zhang, Cai; Zhang, Xiangyu; Wang, Jiming; Zhao, Liyu; Zhao, Dongmei; Cheng, Maosheng published an article in Bioorganic Chemistry. The title of the article was 《Design, synthesis and biological evaluation of 2-aminopyrimidine-based LSD1 inhibitors》.Safety of 2,4-Dichloropyrimidine The author mentioned the following in the article:

AZD9291, with excellent pharmaceutical properties, has been reported to have certain LSD1 inhibitory activity. Therefore, we carried out structural optimization based on the AZD9291 skeleton to increase the LSD1 inhibitory potential of the compound Then, a series of 2-aminopyrimidine derivatives were designed and synthesized as LSD1 inhibitors, and their structure-activity relationships were studied. The most promising compound, X43, with an IC50 of 0.89 μM showed remarkable LSD1 selectivity not only to EGFRwt (>100-fold) but also to MAO-A/B (>50-fold). Further studies showed that X43 inhibited LSD1 activity and induced the apoptosis of A549 cells in a dose-dependent manner. Meanwhile, compound X43 showed a superior ability to inhibit the proliferation of A549 and THP-1 cells, with IC50 values of 1.62 μM and 1.21 μM, resp. Then, analyses of the stability of human liver microsomes, CYP inhibition and in vivo pharmacokinetics in rats showed that X43 had favorable profiles in vitro and in vivo and the potential for further study. Our findings suggested that a 2-aminopyrimidine-based LSD1 inhibitor deserves further investigation as a treatment for LSD1-overexpressing cancer.2,4-Dichloropyrimidine(cas: 3934-20-1Safety of 2,4-Dichloropyrimidine) was used in this study.

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.Safety of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Scattolin, Thomas; Gharbaoui, Tawfik; Chen, Cheng-yi published an article in Organic Letters. The title of the article was 《A Nucleophilic Deprotection of Carbamate Mediated by 2-Mercaptoethanol》.Synthetic Route of C4H2Cl2N2 The author mentioned the following in the article:

Carbamates, typically used for the protection of amines, including Cbz, Alloc, and Me carbamate, was readily deprotected by treatment with 2-mercaptoethanol in the presence of potassium phosphate tribasic in N,N-dimethylacetamide at 75°C. This nucleophilic deprotection protocol was superior to the standard hydrogenolysis or Lewis acid-mediated deprotection conditions for substrates bearing a functionality sensitive to these more traditional methods.2,4-Dichloropyrimidine(cas: 3934-20-1Synthetic Route of C4H2Cl2N2) was used in this study.

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.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Feng, Da; Wei, Fenju; Sun, Yanying; Sharma, Prem Prakash; Zhang, Tao; Lin, Hao; Rathi, Brijesh; De Clercq, Erik; Pannecouque, Christophe; Kang, Dongwei; Zhan, Peng; Liu, Xinyong published their research in Chinese Chemical Letters in 2021. The article was titled 《Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation》.Synthetic Route of C4H2Cl2N2 The article contains the following contents:

Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19-9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10J acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837μmol/L. Furthermore, mol. dynamics simulation indicated that 10j was proposed as a promising mol. for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead mol. for further modification to address virus-drug resistance. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Synthetic Route of C4H2Cl2N2)

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.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia