Category: pyrimidines

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

Wang, Xiao-Jun; Xu, Yibo; Zhang, Li; Krishnamurthy, Dhileepkumar; Senanayake, Chris H. published an article in Organic Letters. The title of the article was 《Mild Iodine-Magnesium Exchange of Iodoaromatics Bearing a Pyrimidine Ring with Isopropylmagnesium Chloride》.Reference of 3-(Pyrimidin-5-yl)benzaldehyde The author mentioned the following in the article:

(Iodo)arenes bearing a reactive pyrimidine ring underwent a clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence of bis[2-(dimethylamino)ethyl] ether to provide the corresponding Grignard reagents. The presence of bis[2-(dimethylamino)ethyl] ether prevented reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As a result, the newly formed reactive Grignard reagents were allowed to react with electrophiles in a highly selective manner to afford adducts in excellent yields. In the experimental materials used by the author, we found 3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6Reference of 3-(Pyrimidin-5-yl)benzaldehyde)

3-(Pyrimidin-5-yl)benzaldehyde(cas: 640769-70-6) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Reference of 3-(Pyrimidin-5-yl)benzaldehydeThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kawakami, Hiroshi; Ebata, Takashi; Koseki, Koshi; Matsumoto, Katsuya; Matsushita, Hajime; Naoi, Yoshitake; Itoh, Kazuo published their research in Heterocycles on December 1 ,1991. The article was titled 《Synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides utilizing coupling reactions between nucleic bases and phenylthio-substituted 2,3-dideoxyribose》.Formula: C17H16N2O5 The article contains the following contents:

Stereoselectivities in coupling reactions between silylated pyrimidine bases I (X = O, R = H, Me; X = NAc, R = H) and 3- or 2-α-phenylthio-2,3-dideoxyribose derivatives, e.g., II (R1 = Cl, OAc) and III, resp., was examined In the former case, no stereoselectivities were observed when the coupling reactions were performed either with 1-chloro sugar in an SN2 mode or in the presence of Lewis acids as catalyst in an SN1 mode. Coupling reaction with 2-α-phenylthio-2,3-dideoxyribose in the presence of Lewis acids, especially SnCl4, proceeded with good stereoselectivity to give anomeric mixtures of nucleosides, e.g. IV, α:β = 1:9. All these nucleosides were converted to 2′,3′-didehydro-2′,3′-dideoxynucleosides, such as V, by oxidation to sulfoxides followed by thermal elimination of sulfenic acid. In the experimental materials used by the author, we found ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Formula: C17H16N2O5)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) 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.Formula: C17H16N2O5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

De Abrew, K. Nadira; Shan, Yuqing K.; Wang, Xiaohong; Krailler, Jesse M.; Kainkaryam, Raghunandan M.; Lester, Cathy C.; Settivari, Raja S.; LeBaron, Matthew J.; Naciff, Jorge M.; Daston, George P. published an article in Toxicology. The title of the article was 《Use of connectivity mapping to support read across: A deeper dive using data from 186 chemicals, 19 cell lines and 2 case studies》.Application In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine The author mentioned the following in the article:

The authors previously demonstrated that the Connectivity Map (CMap) (Lamb et al., 2006) concept can be successfully applied to a predictive toxicol. paradigm to generate meaningful MoA-based connections between chems. (De Abrew et al., 2016). Here the authors expand both the chem. and biol. (cell lines) domain for the method and demonstrate two applications, both in the area of read across. In the first application the authors demonstrate CMap’s utility as a tool for testing biol. relevance of source chems. (analogs) during a chem. led read across exercise. In the second application CMap can be used to identify functionally relevant source chems. (analogs) for a structure of interest (SOI)/target chem. with minimal knowledge of chem. structure. Finally, the authors highlight four factors: promiscuity of chem., dose, cell line and timepoint as having significant impact on the output. The authors discuss the biol. relevance of these four factors and incorporate them into a work flow. The experimental part of the paper was very detailed, including the reaction process of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8Application In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine)

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(cas: 213743-31-8) 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.Application In Synthesis of 7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia