Pyrimidines

In 2018,European Journal of Organic Chemistry included an article by Bruening, Fabian; Katayev, Dmitry; Togni, Antonio. Synthetic Route of C4HCl3N2. The article was titled 《Facile and Efficient Synthesis of 3-Pyrimidinyl Oxindoles by Phase-Transfer-Catalyzed Regioselective Nucleophilic Aromatic Substitution》. The information in the text is summarized as follows:

Phase-transfer-catalyzed regioselective nucleophilic aromatic substitution of 2,4-dichloropyrimidines with N-Boc-protected 3-substituted oxindoles is reported. The reaction allows the formation of unsym. all- carbon quaternary centers in the benzylic position of heteroaromatic scaffolds and proceeds with high chem. yield and excellent functional-group tolerance. Various activated heteroaryl chlorides including dichloropyridazine and activated chloropyridines can also be reacted under the reaction conditions. The experimental part of the paper was very detailed, including the reaction process of 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

In 2019,Journal of the American Chemical Society included an article by Pisa, Rudolf; Cupido, Tommaso; Kapoor, Tarun M.. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine. The article was titled 《Designing Allele-Specific Inhibitors of Spastin, a Microtubule-Severing AAA Protein》. The information in the text is summarized as follows:

The bump-hole approach is a powerful chem. biol. strategy to specifically probe the functions of closely related proteins. However, for many protein families, such as the ATPases associated with diverse cellular activities (AAA), we lack structural data for inhibitor-protein complexes to design allele-specific chem. probes. Here we report the X-ray structure of a pyrazolylaminoquinazoline-based inhibitor bound to spastin, a microtubule-severing AAA protein, and characterize the residues involved in inhibitor binding. We show that an inhibitor analog with a single-atom hydrogen-to-fluorine modification can selectively target a spastin allele with an engineered cysteine mutation in its active site. We also report an X-ray structure of the fluoro analog bound to the spastin mutant. Furthermore, analyses of other mutant alleles suggest how the stereoelectronics of the fluorine-cysteine interaction, rather than sterics alone, contribute to the inhibitor-allele selectivity. This approach could be used to design allele-specific probes for studying cellular functions of spastin isoforms. Our data also suggest how tuning stereoelectronics can lead to specific inhibitor-allele pairs for the AAA superfamily. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

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. Name: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,ACS Applied Materials & Interfaces included an article by Shafikov, Marsel Z.; Daniels, Ruth; Pander, Piotr; Dias, Fernando B.; Williams, J. A. Gareth; Kozhevnikov, Valery N.. Application In Synthesis of 4,6-Dichloropyrimidine. The article was titled 《Dinuclear Design of a Pt(II) Complex Affording Highly Efficient Red Emission: Photophysical Properties and Application in Solution-Processible OLEDs》. The information in the text is summarized as follows:

The light-emitting efficiency of luminescent materials is invariably compromised on moving to the red and near-IR regions of the spectrum due to the transfer of electronic excited-state energy into vibrations. The authors describe how this undesirable energy gap law can be sidestepped for phosphorescent organometallic emitters through the design of a mol. emitter that incorporates two Pt(II) centers. The dinuclear cyclometalated complex of a substituted 4,6-bis(2-thienyl)pyrimidine emits very brightly in the red region of the spectrum (λmax = 610 nm, Φ = 0.85 in deoxygenated CH2Cl2 at 300 K). The lowest-energy absorption band is extraordinarily intense for a cyclometalated metal complex: at λ = 500 nm, ε = 53,800 M-1 cm-1. The very high efficiency of emission achieved can be traced to an unusually high rate constant for the T1 → S0 phosphorescence process, allowing it to compete effectively with nonradiative vibrational decay. The high radiative rate constant correlates with an unusually large zero-field splitting of the triplet state, which is 40 cm-1 by variable-temperature time-resolved spectroscopy over the range 1.7 < T < 120 K. The compound was successfully tested as a red phosphor in an organic light-emitting diode prepared by solution processing. The results highlight a potentially attractive way to develop highly efficient red and NIR-emitting devices through the use of multinuclear complexes. In the experimental materials used by the author, we found 4,6-Dichloropyrimidine(cas: 1193-21-1Application In Synthesis of 4,6-Dichloropyrimidine)

4,6-Dichloropyrimidine(cas: 1193-21-1) 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 4,6-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Design, synthesis and biological evaluation of AZD9291 derivatives as selective and potent EGFRL858R/T790M inhibitors》 were Zhao, Bingbing; Xiao, Zhen; Qi, Jianguo; Luo, Rong; Lan, Zhou; Zhang, Yanzhuo; Hu, Xiaohan; Tang, Qidong; Zheng, Pengwu; Xu, Shan; Zhu, Wufu. And the article was published in European Journal of Medicinal Chemistry in 2019. Application In Synthesis of 2,4-Dichloropyrimidine The author mentioned the following in the article:

Third-generation epidermal growth factor receptor (EGFR)L858R/T790M inhibitors are still the main drugs for the treatment of advanced non-small cell lung cancer (NSCLC), and these drugs have achieved remarkable clin. efficacy. However, there are still many patients suffering from drug-resistant mutations and drug side effects caused by NSCLC. In this study, guided by the mol. simulation, we applied a structure-based drug design strategy (SBDD) and optimized the structure to obtain a series of potent and selective EGFRL858R/T790M inhibitors. The most potent compound 18e demonstrated excellent kinase inhibitory activity and selectivity for EGFRL858R/T790M double mutants and the IC50 value reached nanomolar level. The selectivity of 18e against wild-type EGFR was near to 200-fold. In addition, compound 18e also inhibited H1975 cells proliferation at G2/M phase and induced apoptosis at a concentration of 0.25 μM, which makes it more valuable for potential lung cancer research. In the part of experimental materials, we found many familiar compounds, such as 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

The author of 《I-8, a novel inhibitor of mutant IDH1, inhibits cancer progression in vitro and in vivo》 were Jia, Panli; Wu, Yao; Du, Hongzhi; Yang, Lijun; Zhang, Zhibo; Ma, Tianfang; Li, Sun; Yuan, Shengtao; Lu, Ligong; Zha, Xiaoming. And the article was published in European Journal of Pharmaceutical Sciences in 2019. Application In Synthesis of 2,4-Dichloropyrimidine The author mentioned the following in the article:

Isocitrate dehydrogenase 1 mutations have been discovered in an array of hematol. malignancies and solid tumors. These mutations could cause the production of high levels of 2-hydroxyglutarate, which in turn implicated in epigenetic changes and impaired cell differentiation. Here, we described the characterization of compound I-8, a novel mutant IDH1 inhibitor, both in vitro and in vivo. Compound I-8 specifically inhibited 2-HG production, reduced histone methylation levels, induced differentiation and depleted stem characteristics in engineered and endogenous IDH1 mutant cells. In addition, oral administration of I-8 also significantly suppressed 2-HG production and histone methylation with dose of 150 mg/kg. And I-8 treatment also could induce differentiation and attenuate stem characteristics in tumor tissue. Together, these studies indicated that compound I-8 has clin. potential in tumor therapies as a effective mutant IDH1 inhibitor, and provided scientific guidance for the development of mutant IDH1 inhibitor in the future. In addition to this study using 2,4-Dichloropyrimidine, there are many other studies that have used 2,4-Dichloropyrimidine(cas: 3934-20-1Application In Synthesis 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.Application In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Jiang, Xiangyi; Huang, Boshi; Olotu, Fisayo A.; Li, Jing; Kang, Dongwei; Wang, Zhao; De Clercq, Erik; Soliman, Mahmoud E. S.; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Exploiting the tolerant region I of the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding pocket. Part 2: Discovery of diarylpyrimidine derivatives as potent HIV-1 NNRTIs with high Fsp3 values and favorable drug-like properties》.Name: 2,4-Dichloropyrimidine The article contains the following contents:

A series of novel diarylpyrimidine derivatives I [R1 = cyano, 2-cyanovinyl; R = thiomorpholino, 1-oxo-1,4-thiazinan-4-yl, 1,1-dioxo-1,4-thiazinan-4-yl, etc.] targeted the tolerant region I of the NNRTI binding pocket were designed, synthesized and biol. evaluated as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with favorable drug-like properties was studied. The most active inhibitor I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] exhibited outstanding antiviral activity against most of the viral panel, being about 2-fold (wild-type, EC50 = 0.0021μM), 1.7-fold (K103N, EC50 = 0.0019μM), and slightly more potent (E138K, EC50 = 0.0075μM) than the NNRTI drug etravirine (ETR). Addnl., I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] was endowed with relatively low cytotoxicity (CC50 = 18.52μM). More importantly, I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] possessed improved drug-like properties compared to those of ETR with an increased F sp3 (Fraction of sp3 carbon atoms) value. Furthermore, the mol. dynamics simulation and mol. docking studies were implemented to reveal the binding mode of I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] in the binding pocket. Taken together, I [R1 = 2-cyanovinyl; R = 1,1-dioxo-1,4-thiazinan-4-yl] was a promising lead compound that was worth further investigation. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Name: 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.Name: 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chen, Tianpeng; Wei, Yingying; Zhu, Gaoyang; Zhao, Huajun; Zhang, Xingxian published an article in 2021. The article was titled 《Design, synthesis and structure-activity relationship studies of 4-indole-2-arylaminopyrimidine derivatives as anti-inflammatory agents for acute lung injury》, and you may find the article in European Journal of Medicinal Chemistry.Computed Properties of C4H2Cl2N2 The information in the text is summarized as follows:

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), a clin. high mortality disease, has not been effectively treated till now, and the development of anti-acute lung injury drugs is imminent. Acute lung injury was efficiently treated by inhibiting the cascade of inflammation, and reducing the inflammatory response in the lung. A series of novel compounds with highly efficient inhibiting the expression of inflammatory factors were designed by using 4-indolyl-2-aminopyrimidine as the core skeleton. Totally eleven 4-indolyl-2-arylaminopyrimidine derivatives were designed and synthesized. As well, the related anti-ALI activity of these compounds was evaluated. Compounds I and II showed a superior activity among these compounds, and the inhibition rate of IL-6 and IL-8 release ranged from 62% to 77%, and from 65% to 72%, resp. Furthermore, most of compounds had no significant cytotoxicity in vitro. The infiltration of inflammatory cells into lung tissue significantly reduced by using compound II (20 mg/kg) in the ALI mice model, which achieved the effect of protecting lung tissue and improving ALI. In addition, the inflammatory response was inhibited by using compound II through inhibiting phosphorylation of p-38 and ERK in MAPK signaling pathway, and resulted in protective effect on ALI. These data indicated that compound II showed good anti-inflammatory activity in vitro and in vivo, which was expected to become a leading compound for the treatment of ALI. In the experiment, the researchers used many compounds, for example, 2,4-Dichloropyrimidine(cas: 3934-20-1Computed Properties of C4H2Cl2N2)

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.Computed Properties of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Barbosa da Silva, Elany; Rocha, Debora A.; Fortes, Isadora S.; Yang, Wenqian; Monti, Ludovica; Siqueira-Neto, Jair L.; Caffrey, Conor R.; McKerrow, James; Andrade, Saulo F.; Ferreira, Rafaela S. published an article in 2021. The article was titled 《Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.Reference of 2,4-Dichloropyrimidine The information in the text is summarized as follows:

The cysteine proteases, cruzain and TbrCATL (rhodesain), are therapeutic targets for Chagas disease and Human African Trypanosomiasis, resp. Among the known inhibitors for these proteases, N4-benzyl-N2-phenylquinazoline-2,4-diamine (1a I [R1 = phenyl; R2 = benzyl] in this study), as a competitive cruzain inhibitor (Ki = 1.4μM) was described. The synthesis and biol. evaluation of 22 analogs I [R1 = Ph, 4-OH-Ph, 2-pyridyl; R2 = benzyl, Ph, 3-Cl-Ph, etc] of I [R1 = phenyl; R2 = benzyl], containing modifications in the quinazoline core, and in the substituents in positions 2 and 4 of this ring was described. The analogs I demonstrate low micromolar inhibition of the target proteases and cidal activity against Trypanosoma cruzi with up to two log selectivity indexes in counterscreens with myoblasts. Fourteen compounds were active against Trypanosoma brucei at low to mid micromolar concentrations During the optimization of I [R1 = phenyl; R2 = benzyl], structure-based design and prediction of physicochem. properties were employed to maintain potency against the enzymes while removing colloidal aggregator characteristics observed for some mols. in this series.2,4-Dichloropyrimidine(cas: 3934-20-1Reference 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.Reference of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Yang, Tingting; Zhang, Wenjuan; Cao, Shengjie; Sun, Shiyang; Cai, Xu; Xu, Lei; Li, Pengyun; Zheng, Zhibing; Li, Song published an article in European Journal of Medicinal Chemistry. The title of the article was 《Discovery of highly potent and selective EGFRT790M/L858R TKIs against NSCLC based on molecular dynamic simulation》.Synthetic Route of C4H2Cl2N2 The author mentioned the following in the article:

Epidermal growth factor receptor (EGFR) is the most attractive target for drug research in non-small cell lung cancer (NSCLC). There have been three generation drugs developed to treat of NSCLC. The third-generation EGFR tyrosine kinase inhibitors (TKIs) Rociletinib and Osimertinib (AZD9291) achieved remarkable clin. efficacy. However, due to the inhibitory activity against the wild-type EGFR, the side effect of associated skin rash and gastrointestinal toxicity appeared. Thus, there is still an urgent need to develop novel inhibitors with potent inhibitory activity and high selectivity for T790M-containing EGFR over EGFRWT. Herein, guided by the mol. dynamic simulation results, a series of potent and selective Osimertinib derivatives were designed, synthesized and evaluated. The promising compounds N-(2-((2-((4-bromobenzyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-acrylamido-5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)-4-bromo-N-methylbenzamide, N-(2-((2-acrylamido-5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)-N-methyl-but-2-ynamide, N-(4-methoxy-2-(methyl(2-(methyl(prop-2-yn-1-yl)amino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide and N-(2-((2-(benzyl(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide demonstrated excellent kinase inhibitory activity and high selectivity for EGFRT790M/L858R mutant. The selectivity of N-(2-((2-((4-bromobenzyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide to EGFRT790M/L858R was the highest in the current known compounds near to 2500-fold. In addition, the compound N-(2-((2-((4-bromobenzyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide showed considerable activity against NCI-H1975 and HCC827 cells, arrested NCI-H1975 cell cycle at the G2/M stage and significantly induced apoptosis in NCI-H1975 cell. These encouraged results indicated that N-(2-((2-((4-bromobenzyl)(methyl)amino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide will be used as a candidate targeting EGFRT790M/L858R for further pharmacodynamic and pharmacokinetic studies, and all these studies provide important clues for the discovery of potent EGFRT790M/L858R inhibitors with high selectivity. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Synthetic Route of C4H2Cl2N2)

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.Synthetic Route of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2020 ,《Purine/purine isoster based scaffolds as new derivatives of benzamide class of HDAC inhibitors》 appeared in European Journal of Medicinal Chemistry. The author of the article were Nepali, Kunal; Chang, Ting-Yu; Lai, Mei-Jung; Hsu, Kai-Cheng; Yen, Yun; Lin, Tony Eight; Lee, Sung-Bau; Liou, Jing-Ping. The article conveys some information:

This study reports the design, synthesis and evaluation of a series of histone deacetylase (HDAC) inhibitors I (X = Cl, methylazanyl, (3-chloro-4-fluorophenyl)azanyl, etc.; Y = Cl, NH2, (2,4,6-trichloro-3,5-dimethoxyphenyl)azanyl; Z = N, CH; R = H, F) containing purine/purine isoster as a capping group and an N-(2-aminophenyl)-benzamide unit. In vitro cytotoxicity studies reveal that benzamide I (X = (3-chloro-4-fluorophenyl)azanyl; Y = NH2; Z = N; R = H) (A) suppressed the growth of triple-neg. breast cancer cells MDA-MB-231 (IC50 = 1.48μM), MDA-MB-468 (IC50 = 0.65μM), and liver cancer cells HepG2 (IC50 = 2.44μM), better than MS-275 and Chidamide. Compared to the well-known HDAC inhibitor SAHA, (A) showed a higher toxicity (IC50 = 0.33μM) in three leukemic cell lines, K-562, KG-1 and THP-1. Moreover, (A) was found to be equally virulent in the HDAC-sensitive and -resistant gastric cell lines, YCC11 and YCC3/7, resp., indicating the potential of (A) to overcome HDACi resistance. Furthermore, substantial inhibitory effects more pronounced than MS-275 and Chidamide were displayed by (A) towards HDAC1, 2 and 3 isoforms with IC50 values of 0.108, 0.585 and 0.563μM resp. Compound (A) also exhibited a potent antitumor efficacy in human MDA-MB-231 breast cancer xenograft mouse model, providing a potential lead for the development of anticancer agents. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

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. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia