Category: 3934-20-1

《Improvement of aqueous solubility of lapatinib-derived analogues: identification of a quinolinimine lead for human African trypanosomiasis drug development》 was written by Bachovchin, Kelly A.; Sharma, Amrita; Bag, Seema; Klug, Dana M.; Schneider, Katherine M.; Singh, Baljinder; Jalani, Hitesh B.; Buskes, Melissa J.; Mehta, Naimee; Tanghe, Scott; Momper, Jeremiah D.; Sciotti, Richard J.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Pollastri, Michael P.; Ferrins, Lori. Quality Control of 2,4-DichloropyrimidineThis research focused ontrypanosomiasis parasiticide quinolinimine lapatinib pharmacokinetics Trypanosoma brucei. The article conveys some information:

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in I, which was part of a series typically associated with poor aqueous solubility In this report, we present various medicinal chem. strategies that were used to increase the aqueous solubility and improve the physicochem. profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC50)) was established, as part of the lead selection process. Increasing the sp3 carbon content of I resulted in II (0.19 μM EC50 against T. brucei and 990 μM aqueous solubility). Further chem. exploration of II yielded III, a trypanocidal quinolinimine (EC50: 0.013 μM; aqueous solubility: 880 μM; and CEC50: 0.18 μM). Compound III reduced parasitemia 109 fold in trypanosome-infected mice; it is an advanced lead for HAT drug development. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Quality Control 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.Quality Control of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Quality Control of 2,4-DichloropyrimidineIn 2021 ,《Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer》 appeared in European Journal of Medicinal Chemistry. The author of the article were Yang, Huali; Wang, Xiaobing; Wang, Cheng; Yin, Fucheng; Qu, Lailiang; Shi, Cunjian; Zhao, Jinhua; Li, Shang; Ji, Limei; Peng, Wan; Luo, Heng; Cheng, Maosheng; Kong, Lingyi. The article conveys some information:

NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound I, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, I suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Quality Control 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.Quality Control of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Patterson, Jaclyn R.; Graves, Alan P.; Stoy, Patrick; Cheung, Mui; Desai, Tina A.; Fries, Harvey; Gatto, Gregory J. Jr.; Holt, Dennis A.; Shewchuk, Lisa; Totoritis, Rachel; Wang, Liping; Kallander, Lara S. published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Identification of Diarylurea Inhibitors of the Cardiac-Specific Kinase TNNI3K by Designing Selectivity Against VEGFR2, p38α, and B-Raf》.Product Details of 3934-20-1 The article contains the following contents:

A series of diarylurea inhibitors of the cardiac-specific kinase TNNI3K were developed to elucidate the biol. function of TNNI3K and evaluate TNNI3K as a therapeutic target for the treatment of cardiovascular diseases. Utilizing a structure-based design, enhancements in kinase selectivity were engineered into the series, capitalizing on the established X-ray crystal structures of TNNI3K, VEGFR2, p38α, and B-Raf. Our efforts culminated in the discovery of an in vivo tool compound 47 (GSK329), which exhibited desirable TNNI3K potency and rat pharmacokinetic properties as well as promising kinase selectivity against VEGFR2 (40-fold), p38α (80-fold), and B-Raf (>200-fold). Compound 47 demonstrated pos. cardioprotective outcomes in a mouse model of ischemia/reperfusion cardiac injury, indicating that optimized exemplars from this series, such as 47, are favorable leads for discovering novel medicines for cardiac diseases. In addition to this study using 2,4-Dichloropyrimidine, there are many other studies that have used 2,4-Dichloropyrimidine(cas: 3934-20-1Product Details of 3934-20-1) 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.Product Details of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Triptycene based and nitrogen rich hyper cross linked polymers (TNHCPs) as efficient CO2 and iodine adsorbent》 was written by Hassan, Atikur; Goswami, Santu; Alam, Akhtar; Bera, Ranajit; Das, Neeladri. Application In Synthesis of 2,4-DichloropyrimidineThis research focused ontriptycene pyrazine copolymer crosslinked radioactive waste iodine adsorbent; carbon dioxide adsorption air pollution reusable recyclable. The article conveys some information:

Triptycene based polymeric networks are rapidly emerging as porous organic polymers (POPs) for efficient capture of small gas mols. Further, such triptycene based frameworks are also being explored as adsorbents for radioactive iodine. Herein, a group of three unique “”Triptycene based and Nitrogen-rich Hyper Crosslinked Polymers”” (TNHCPs) have been easily obtained via the well-known Friedel-Craft alkylation reactions of triptycene with six-membered N-rich heterocycles. In these TNHCPs, the presence of triptycene motifs yields contorted and rigid polymeric frameworks with plenty of micropores and ultramicropores. Further, the presence of N-rich heterocycles increases their efficiency to selectively capture carbon dioxide and adsorb iodine vapors as well as iodide ions from aqueous solutions Comparison with data in recent literature reveals that TNHCPs are better in these domains than several previously reported POPs in general and HCPs in particular. In the experiment, the researchers used 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 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.Application In Synthesis of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 3934-20-1In 2021 ,《Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design》 was published in European Journal of Medicinal Chemistry. The article was written by Wang, Linxiao; Zhang, Qian; Wang, Zhe; Zhu, Wufu; Tan, Ninghua. The article contains the following contents:

Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine I [X = C, C=O; Y = H, N(Me)2, N(Et)2] II [R = H, Me; R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, indolin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl] III and N-methylpicolinamide derivatives IV [R2 = pyrrolidin-1-yl, 1-piperidyl, morpholino, 3,4-dihydro-1H-isoquinolin-2-yl] substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds I, II, III, IV showed selectivity toward the A549 cell lines and the most promising compound IV [R2 = 1-piperidyl] could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84μM. Moreover, IV [R2 = 1-piperidyl] could induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound IV [R2 = 1-piperidyl] could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. The studies of docking, mol. dynamics, MM/PBSA and frequency anal. theor. supported the conclusions of the bioevaluation. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Related Products of 3934-20-1)

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.Related Products of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Product Details of 3934-20-1In 2020 ,《Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Sui, Yan-Fei; Li, Di; Wang, Juan; Bheemanaboina, Rammohan R. Yadav; Ansari, Mohammad Fawad; Gan, Lin-Ling; Zhou, Cheng-He. The article conveys some information:

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target mols. were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 μg/mL. The active mol. 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramol. complex, which might be responsible for its antimicrobial action. The further investigation showed that this mol. could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force. In the experimental materials used by the author, we found 2,4-Dichloropyrimidine(cas: 3934-20-1Product Details of 3934-20-1)

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.Product Details of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Huang, Daowei; Yang, Jixia; Zhang, Qingwei; Wang, Guan; Zhang, Zixue; Zhang, Yue; Li, Jianqi published an article in 2021. The article was titled 《Structure-guided design and development of novel N-phenylpyrimidin-2-amine derivatives as potential c-Met inhibitors》, and you may find the article in European Journal of Medicinal Chemistry.Recommanded Product: 3934-20-1 The information in the text is summarized as follows:

The HGF/Met signaling pathway is over-expressed in many types of cancers and closely related to oncogenesis and metastasis. Thus, we developed novel N-phenylpyrimidin-2-amine derivatives to test their inhibitory activities towards c-Met kinase, and most of the compounds (15a-i, 15o-r, 20 and 34a-c) could inhibit the target with IC50 values from 550.8 nM to 15.0 nM. Subsequently, compound 15b, 15d, 15f, 15i, 15o, 15r, 20, 34a and 34b also showed high antiproliferative activities in c-Met sensitive tumor cell lines (PC-3, Panc-1, HepG2, HCT116 and Caki-1) with IC50 values from 0.53 to 1.37 μM. The lead compound 34a displayed outstanding c-Met inhibitory activity (IC50: 15.0 nM) and antiproliferative activities. Furthermore, 34a also performed favorable pharmacokinetic properties in mice (F%: 59.3) and an acceptable safety profile in preclin. studies. Further docking studies showed a common interaction of 34a with c-Met at the ATP-binding site, which indicated that 34a could be a potential candidate for c-Met inhibitors. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Recommanded Product: 3934-20-1)

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.Recommanded Product: 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane》 was written by Fan, Tingting; Guo, Weikai; Shao, Ting; Zhou, Wenbo; Hu, Pan; Liu, Mingyao; Chen, Yihua; Yi, Zhengfang. Application of 3934-20-1 And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

A series of phenylthiazole and phenylthiophene pyrimidindiamine derivatives l [R1 = ethylamino, propylamino, butylamino, pyrrolidino; R2 = H, OMe, F, Cl, Br, etc.] were designed and synthesized by modifying the hit compound (N2-isobutyl-N4-((4-methyl-2-phenylthiazol-5-yl)methyl) pyrimidine-2,4-diamine) and their antibacterial activities were evaluated both in-vitro and in-vivo was reported. Among the tested compounds, compound I [R1 = isobutylamino; R2 = 3-bromo] displayed the best antibacterial activities, which was not only capable of inhibiting E. coli and S. aureus growth at concentrations as low as 2 and 3μg/mL in-vitro, but also efficacious in a mice model of bacteremia in vivo. Unlike conventional antibiotics, compound I [R1 = isobutylamino; R2 = 3-bromo] was elucidated to mainly destroy the bacterial cell membrane, with the dissipation of membrane potential and leakage of contents, ultimately leading to cell death. The destruction of cell structure was challenging to induce bacterial resistance, which suggested that compound I [R1 = isobutylamino; R2 = 3-bromo] was a promising alternatives to antibiotics against bacteria. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Application of 3934-20-1)

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 of 3934-20-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2019,Reaction Chemistry & Engineering included an article by Hone, Christopher A.; Boyd, Alistair; O’Kearney-McMullan, Anne; Bourne, Richard A.; Muller, Frans L.. Name: 2,4-Dichloropyrimidine. The article was titled 《Definitive screening designs for multistep kinetic models in flow》. The information in the text is summarized as follows:

Currently, rate-based understanding of organic reactions employed in the manufacture of active pharmaceutical ingredients (APIs) is often not obtained. In many cases, the generation of kinetic models is still seen as a specialised and time intensive activity, which can only be justified at certain instances in development. In this Communication, we report the application of a definitive screening design (DSD) in combination with reaction profiling for the efficient collection of kinetic data. The exptl. data (10 profiles, 40 exptl. data points) were collected within a short time frame (< 1 wk) within a continuous flow reactor. The data were fitted to a multistep kinetic model consisting of 3 fitted rate constants and 3 fitted activation energies. The approach is demonstrated on a Friedel-Crafts type reaction used in the synthesis of an important API. Our approach enables early identification of the sensitivity of product quality to parameter changes and the early use of process models to identify optimal process-equipment combinations in silico, significantly reducing development time and scale-up risks. After reading the article, we found that the author used 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

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