Tag: 100-200

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

Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineIn 2015 ,《Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology》 appeared in ACS Medicinal Chemistry Letters. The author of the article were Johannes, Jeffrey W.; Almeida, Lynsie; Barlaam, Bernard; Boriack-Sjodin, P. Ann; Casella, Robert; Croft, Rosemary A.; Dishington, Allan P.; Gingipalli, Lakshmaiah; Gu, Chungang; Hawkins, Janet L.; Holmes, Jane L.; Howard, Tina; Huang, Jian; Ioannidis, Stephanos; Kazmirski, Steven; Lamb, Michelle L.; McGuire, Thomas M.; Moore, Jane E.; Ogg, Derek; Patel, Anil; Pike, Kurt G.; Pontz, Timothy; Robb, Graeme R.; Su, Nancy; Wang, Haiyun; Wu, Xiaoyun; Zhang, Hai-Jun; Zhang, Yue; Zheng, Xiaolan; Wang, Tao. The article conveys some information:

The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germline mutations of several Wnt pathway components, such as Axin, APC, and ss-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclin. models of cancer and its impact on normal tissue, the authors sought a small mol. inhibitor of TNKS1/2 with suitable physicochem. properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-Ph quinazolinone hit I, the authors discovered the pyrrolopyrimidinone compound II (AZ6102), which is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound II can be formulated well in a clin. relevant i.v. solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclin. species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms. The results came from multiple reactions, including the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application In Synthesis 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. 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 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Name: 2,4,6-TrichloropyrimidineIn 2016 ,《Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Hu, Jianping; Wang, Xin; Chen, Lin; Huang, Min; Tang, Wei; Zuo, Jianping; Liu, Yu-Chih; Shi, Zhe; Liu, Rongfeng; Shen, Jingkang; Xiong, Bing. The article conveys some information:

The histone methylation on lysine residues is one of the most studied posttranslational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure-activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, the authors initialized a medicinal chem. modification based on the GSK-J1 structure. Finally, the authors found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The Et ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-α production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 2,4,6-Trichloropyrimidine)

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.Name: 2,4,6-Trichloropyrimidine

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

In 2022,Hua, Yi; Fang, Xiaobao; Xing, Guomeng; Xu, Yuan; Liang, Li; Deng, Chenglong; Dai, Xiaowen; Liu, Haichun; Lu, Tao; Zhang, Yanmin; Chen, Yadong published an article in Journal of Chemical Information and Modeling. The title of the article was 《Effective reaction-based de novo strategy for kinase targets: A case study on MERTK inhibitors》.Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

Reaction-based de novo design is the computational generation of novel mol. structures by linking building blocks using reaction vectors derived from chem. knowledge. In this work, we first adopted a recurrent neural network (RNN) model to generate three groups of building blocks with different functional groups and then constructed an in silico target-focused combinatorial library based on chem. reaction rules. Mer tyrosine kinase (MERTK) was used as a study case. Combined with a scaffold enrichment anal., 15 novel MERTK inhibitors covering four scaffolds were achieved. Among them, compound 5a obtained an IC50 value of 53.4 nM against MERTK without any further optimization. The efficiency of hit identification could be significantly improved by shrinking the compound library with the fragment iterative optimization strategy and enriching the dominant scaffold in the hinge region. We hope that this strategy can provide new insights for accelerating the drug discovery process. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Application In Synthesis 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. Application In Synthesis of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Wu, Tianxiao; Qin, Qiaohua; Liu, Nian; Zhang, Chu; Lv, Ruicheng; Yin, Wenbo; Sun, Yin; Sun, Yixiang; Wang, Ruifeng; Zhao, Dongmei; Cheng, Maosheng published an article in European Journal of Medicinal Chemistry. The title of the article was 《Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold》.Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Recommanded Product: 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. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Recommanded Product: 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidineThey 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

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

《Mycobacterium tuberculosis Decaprenylphosphoryl-β-D-ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity》 was written by Borthwick, Jennifer A.; Alemparte, Carlos; Wall, Ian; Whitehurst, Benjamin C.; Argyrou, Argyrides; Burley, Glenn; de Dios-Anton, Paco; Guijarro, Laura; Monteiro, Maria Candida; Ortega, Fatima; Suckling, Colin J.; Pichel, Julia Castro; Cacho, Monica; Young, Robert J.. Product Details of 1193-21-1 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:

Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) is an essential enzyme in Mycobacterium tuberculosis and has recently been studied as a potential drug target, with inhibitors progressing to clin. studies. Here we describe the identification of a novel series of morpholino-pyrimidine DprE1 inhibitors. These were derived from a phenotypic high-throughput screening (HTS) hit with suboptimal physicochem. properties. Optimization strategies included scaffold-hopping, synthesis, and evaluation of fragments of the lead compounds and property-focused optimization. The resulting optimized compounds had much improved physicochem. properties and maintained enzyme and cellular potency. These mols. demonstrated potent efficacy in an in vivo tuberculosis murine infection model. After reading the article, we found that the author used 4,6-Dichloropyrimidine(cas: 1193-21-1Product Details of 1193-21-1)

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.Product Details of 1193-21-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies》 was published in Archiv der Pharmazie (Weinheim, Germany) in 2020. These research results belong to Qin, Qiaohua; Wu, Tianxiao; Yin, Wenbo; Sun, Yixiang; Zhang, Xiangyu; Wang, Ruifeng; Guo, Jing; Zhao, Dongmei; Cheng, Maosheng. Synthetic Route of C4HCl3N2 The article mentions the following:

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biol. activity against PAK4. Among the derivatives studied, promising compounds A2, B6, and B8 displayed the highest inhibitory activities against PAK4 (IC50 = 18.4, 5.9, and 20.4 nM, resp.). From the cellular assay, compound B6 exhibited the highest potency with an IC50 value of 2.533μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and mol. docking studies against PAK4. The detailed structure-activity relationship based on the biochem. activities and mol. docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: -7.593 kcal/mol). The mol. docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor. 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