Tag: 100-200

In 2019,Bioorganic & Medicinal Chemistry Letters included an article by Jo, Jeyun; Kim, Heegyu; Oh, Ji Youn; Kim, Soyeong; Park, Yeong Hye; Choi, Hyeonjin; Jeong, Jee-Yeong; Jung, Young-Suk; Yun, Hwayoung. Reference of 2,4-Dichloropyrimidine. The article was titled 《SAR Optimization studies on a novel series of 2-anilinopyrimidines as selective inhibitors against triple-negative breast cancer cell line MDA-MB-468》. The information in the text is summarized as follows:

Two series of 2-anilinopyrimidines I [R1 = pyrrol-1-yl, indol-1-yl, 4-Me-piperidin-1-yl; R2 = NMe2, morpholin-4-yl, thiomorpholin-4-yl, piperidin-1-yl] and II [R3 = methoxy, cyclohexyl; R4 = indol-1-yl, pyrrolidin-1-yl, 4-Cl-piperidin-1-yl, etc.] as a selective inhibitors of the basal-like TNBC cell line MDA-MB-468 were reported. An extensive anal. of structure-activity relationships of the analogs I and II revealed that aminoalkyl groups at the end of the Pr chain are amenable to modification. Compound II [R3 = cyclohexyl; R4 = 4-Cl-piperidin-1-yl] was found to be the most potent and selective and was about three times more potent and selective than I [R1 = 4-Me-piperidin-1-yl; R2 = piperidin-1-yl] was against the TNBC cells. The experimental part of the paper was very detailed, including the reaction process of 2,4-Dichloropyrimidine(cas: 3934-20-1Reference of 2,4-Dichloropyrimidine)

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.Reference of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2015,Samanta, Ramesh C.; Yamamoto, Hisashi published 《Selective Halogenation Using an Aniline Catalyst》.Chemistry – A European Journal published the findings.Electric Literature of C6H3Cl2N3 The information in the text is summarized as follows:

Electrophilic halogenation was used to produce a wide variety of halogenated compounds The arylamines were found to generate an N-halo arylamine intermediate, which acts as a highly reactive but selective catalytic electrophilic halogen source. A wide variety of heteroaromatic and aromatic compounds were halogenated using com. available N-halosuccinimides, for example, NCS, NBS, and NIS, with good to excellent yields and with very high selectivity. In the case of unactivated double bonds, allylic chlorides were obtained under chlorination conditions, whereas bromocyclization occurred for polyolefin. The reactivity of the catalyst could be tuned by varying the electronic properties of the arene moiety of catalyst. In the experiment, the researchers used many compounds, for example, 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

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. Electric Literature of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Related Products of 14001-69-5On May 12, 2022 ,《Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor》 appeared in Journal of Medicinal Chemistry. The author of the article were Miller, Duncan C.; Reuillon, Tristan; Molyneux, Lauren; Blackburn, Timothy; Cook, Simon J.; Edwards, Noel; Endicott, Jane A.; Golding, Bernard T.; Griffin, Roger J.; Hardcastle, Ian; Harnor, Suzannah J.; Heptinstall, Amy; Lochhead, Pamela; Martin, Mathew P.; Martin, Nick C.; Myers, Stephanie; Newell, David R.; Noble, Richard A.; Phillips, Nicole; Rigoreau, Laurent; Thomas, Huw; Tucker, Julie A.; Wang, Lan-Zhen; Waring, Michael J.; Wong, Ai-Ching; Wedge, Stephen R.; Noble, Martin E. M.; Cano, Celine. The article conveys some information:

The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analog with an optimal balance of ERK5 inhibition and oral exposure. In the experiment, the researchers used 2-Methoxy-5-nitropyrimidine(cas: 14001-69-5Related Products of 14001-69-5)

2-Methoxy-5-nitropyrimidine(cas: 14001-69-5) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Related Products of 14001-69-5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Novel N-thioamide analogues of pyrazolylpyrimidine based piperazine: Design, synthesis, characterization, in-silico molecular docking study and biological evaluation》 was written by Vekariya, Mayur K.; Patel, Dhaval B.; Pandya, Pranav A.; Vekariya, Rajesh H.; Shah, Prapti U.; Rajani, Dhanji P.; Shah, Nisha K.. COA of Formula: C4H2Cl2N2This research focused onthioureidopiperazinyl pyrimidinyl pyrazolecarboxylate preparation antitubercular antimalaria antibacterial antifungal activity; structure thioureidopiperazinyl pyrimidinyl pyrazolecarboxylate antitubercular antimalaria antibacterial antifungal activity; mol docking thioureidopiperazinyl pyrimidinyl pyrazolecarboxylate DHFR FabH hydrolase; calculated hERG inhibition biol permeability thioureidopiperazinyl pyrimidinyl pyrazolecarboxylate; solubility polar surface area calculated thioureidopiperazinyl pyrimidinyl pyrazolecarboxylate. The article conveys some information:

(Thioureidopiperazinyl)pyrimidinyl pyrazolecarboxylates I (R = Ph, Me, Et, n-Pr, Bu, i-Pr, t-Bu, H2C:CHCH2, cyclohexyl, PhCH2, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 3-ClC6H4, 4-ClC6H4, 4-FC6H4, 2,4-Cl2C6H3, 3-IC6H4, 4-MeC6H4, PhCO, 4-O2NC6H4, 2,3-Cl2C6H3, 2,6-Cl2C6H3, 2-ClC6H4) were prepared and tested as potential antituberculosis, antimalarial, antibacterial, and antifungal agents. Their physicochem., biol. permeabilities into cells and through the blood-brain barrier, and hERG inhibition were calculated and the binding to Plasmodium falciparum dihydrofolate reductase, Escherichia coli FabH, and Staphylococcus aureus hydrolase were calculated for selected compounds In addition to this study using 4,6-Dichloropyrimidine, there are many other studies that have used 4,6-Dichloropyrimidine(cas: 1193-21-1COA of Formula: C4H2Cl2N2) was used in this study.

4,6-Dichloropyrimidine(cas: 1193-21-1) 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.COA of Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Li, Yingxue; Chang, Yaoyao; Fu, Jianfang; Ding, Rongcai; Zhang, Lingyun; Liang, Tian; Liu, Yajing; Liu, Yue; Hu, Jinxing published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing a 4,5,6,7-tetrahydrothieno [3,2-c]pyridine as potent EGFR inhibitors》.Formula: C4H2Cl2N2 The article contains the following contents:

To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, the principle of collocation was used to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFRT790M) for use as EGFRL858R/T790M kinase inhibitors. The most promising compound N-(5-((5-chloro-4-(6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl)pyrimidin-2-yl) amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propionamide, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFRL858R/T790M, with an IC50 value of 4.0 nM and more than 42-fold selectivity for EGFRWT (IC50 = 170.0 nM). Moreover, the above compound showed strong anti-proliferative activity against H1975 cells, with IC50 value of 0.086μΜ. Addnl., the effective inhibition of cell migration and the promotion of apoptosis by the above compound verified its mechanism of action, as a selective inhibitor of EGFRL858R/T790M. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Formula: 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.Formula: C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer》 was written by Sun, Dejuan; Yang, Zijian; Zhen, Yongqi; Yang, Yushang; Chen, Yanmei; Yuan, Yong; Zhang, Lan; Zeng, Xiaoxi; Chen, Lixia. Recommanded Product: 3934-20-1 And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

5-Bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives were synthesized and evaluated as ULK1 inhibitors in non-small cell lung cancer. Among all the obtained ULK1 inhibitors, 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine, was the most active one. The docking anal. was conducted to compare 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine and SBI-0206965, which further elucidated the roles of the H-bond donor. This compound inhibited the proliferation of A549 cells and showed strong inhibitory activity against ULK1 kinase. Moreover, we found that 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine could induce apoptosis while simultaneously blocking autophagy. Collectively, these findings shed new light on 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine that would be utilized as a promising candidate drug for the future NSCLC therapy. The experimental process involved the reaction of 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

The author of 《Discovery of potent, orally bioavailable ERK1/2 inhibitors with isoindolin-1-one structure by structure-based drug design》 were Ji, Dezhong; Zhang, Lingzhi; Zhu, Qihua; Bai, Ying; Wu, Yaoyao; Xu, Yungen. And the article was published in European Journal of Medicinal Chemistry in 2019. Category: pyrimidines The author mentioned the following in the article:

Constitutive activation of MAPK (RAS/RAF/MEK/ERK) pathway is frequently observed in many tumors and thus has become an interesting therapeutic target for cancer therapy. Despite the successful development of BRAF and MEK inhibitors in clinic treatment, resistance often appears to re-enhance ERK1/2 signaling. Inspired by the central role of the ERK1/2 signaling cascade in cancer, we describe the scaffold-hopping generation of a series of isoindolin-1-one ERK1/2 inhibitors. Our new compounds could inhibit proliferation of KRAS and BRAF mutant cells lines at low nanomolar concentrations Compound 22a possesses acceptable pharmacokinetic profiles and showed considerable in vivo antitumor efficacy in a HCT-116 xenograft model, providing a promising basis for further optimization towards clin. ERK1/2 inhibitors. In the part of experimental materials, we found many familiar compounds, such as 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)

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.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3》 were Li, Yingxiu; Ye, Tianyu; Xu, Le; Dong, Yuhong; Luo, Yong; Wang, Chu; Han, Yufei; Chen, Ke; Qin, Mingze; Liu, Yajing; Zhao, Yanfang. And the article was published in European Journal of Medicinal Chemistry in 2019. Reference of 2,4-Dichloropyrimidine The author mentioned the following in the article:

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “”A”” Ph ring and “”B”” Ph ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor. After reading the article, we found that the author used 2,4-Dichloropyrimidine(cas: 3934-20-1Reference 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.Reference of 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration》 were Cao, Hengyi; Zhu, Guangya; Sun, Lin; Chen, Ge; Ma, Xinxin; Luo, Xiao; Zhu, Jidong. And the article was published in European Journal of Medicinal Chemistry in 2019. Application of 3764-01-0 The author mentioned the following in the article:

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5, (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(7-(trifluoromethyl)4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one [2379528-08-0], exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclin. candidate to treat IDH1-mutant brain tumors. In addition to this study using 2,4,6-Trichloropyrimidine, there are many other studies that have used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Application of 3764-01-0) was used in this study.

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.Application of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2018,Journal of Medicinal Chemistry included an article by Vazquez, Michael L.; Kaila, Neelu; Strohbach, Joseph W.; Trzupek, John D.; Brown, Matthew F.; Flanagan, Mark E.; Mitton-Fry, Mark J.; Johnson, Timothy A.; TenBrink, Ruth E.; Arnold, Eric P.; Basak, Arindrajit; Heasley, Steven E.; Kwon, Soojin; Langille, Jonathan; Parikh, Mihir D.; Griffin, Sarah H.; Casavant, Jeffrey M.; Duclos, Brian A.; Fenwick, Ashley E.; Harris, Thomas M.; Han, Seungil; Caspers, Nicole; Dowty, Martin E.; Yang, Xin; Banker, Mary Ellen; Hegen, Martin; Symanowicz, Peter T.; Li, Li; Wang, Lu; Lin, Tsung H.; Jussif, Jason; Clark, James D.; Telliez, Jean-Baptiste; Robinson, Ralph P.; Unwalla, Ray. Related Products of 90213-66-4. The article was titled 《Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases》. The information in the text is summarized as follows:

Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. The authors’ efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, the authors discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by x-ray crystallog. anal. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clin. candidate for the treatment of JAK1-mediated autoimmune diseases.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4) was used in this study.

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. Related Products of 90213-66-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia