Tag: 400-500

COA of Formula: C22H25ClN6O2On October 1, 2020 ,《Design, synthesis and SAR study of 2-aminopyrimidines with diverse Michael addition acceptors for chemically tuning the potency against EGFRL858R/T790M》 was published in Bioorganic & Medicinal Chemistry. The article was written by Shao, Jiaan; Liu, Shuangrong; Liu, Xingyu; Pan, Youlu; Chen, Wenteng. The article contains the following contents:

Design, synthesis and SAR study of 2-aminopyrimidines I [R1 = H, 3-Me, 2-OMe, etc.; R2 = Me, COMe; R3 = CF3, Cl; X = Me, F, Cl, Ph; Y = CH, N; Z = NH, O] and II with diverse Michael addition acceptors for chem. tuning the potency against EGFRL858R/T790M were described. By perturbing the electronic nature of acrylamide moiety, with a chloro-group at the α-position of the Michael addition acceptor was identified. It was found that I [R1 = H; R2 = COMe; R3 = Cl; X = Cl; Y = CH; Z = NH] retained the excellent EGFRL858R/T790M potency (IC50 = 3.9 nM) and exhibited good anti-proliferative activities against the gefitinib-resistant NCI-H1975 cells (IC50 = 0.75μM). Moreover, I [R1 = H; R2 = COMe; R3 = Cl; X = Cl; Y = CH; Z = NH] displayed a significant EGFRWT selectivity and much weaker inhibitory activity against non-EGFR dependent SW620 cell and COS7. Preliminary study showed that I [R1 = H; R2 = COMe; R3 = Cl; X = Cl; Y = CH; Z = NH] could arrest NCI-H1975 cells in G0/G1 phase. This work provided a promising chem. tuned strategy for balancing the mutant-EGFR potency and selectivity as well as ‘off-target’ toxicity. In the experimental materials used by the author, we found 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1COA of Formula: C22H25ClN6O2)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.COA of Formula: C22H25ClN6O2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Zhou, Wenjun; Ercan, Dalia; Chen, Liang; Yun, Cai-Hong; Li, Danan; Capelletti, Marzia; Cortot, Alexis B.; Chirieac, Lucian; Iacob, Roxana E.; Padera, Robert; Engen, John R.; Wong, Kwok-Kin; Eck, Michael J.; Gray, Nathanael S.; Janne, Pasi A. published their research in Nature (London, United Kingdom) on December 31 ,2009. The article was titled 《Novel mutant-selective EGFR kinase inhibitors against EGFR T790M》.HPLC of Formula: 1213269-26-1 The article contains the following contents:

The clin. efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clin. more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacol. screens against clin. important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors. In addition to this study using 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine, there are many other studies that have used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1HPLC of Formula: 1213269-26-1) was used in this study.

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.HPLC of Formula: 1213269-26-1

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Basu, Debjit; Richters, Andre; Rauh, Daniel published their research in Bioorganic & Medicinal Chemistry on August 1 ,2015. The article was titled 《Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR [Erratum to document cited in CA163:000258]》.Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine The article contains the following contents:

On page 2768, Figure 1B contained an error in structure CO-1686; the corrected figure is given. After reading the article, we found that the author used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Basu, Debjit; Richters, Andre; Rauh, Daniel published their research in Bioorganic & Medicinal Chemistry on August 1 ,2015. The article was titled 《Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR [Erratum to document cited in CA163:000258]》.Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine The article contains the following contents:

On page 2768, Figure 1B contained an error in structure CO-1686; the corrected figure is given. After reading the article, we found that the author used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Recommanded Product: 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

《Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors》 was written by Han, Chun; Wan, Ledong; Ji, Hongbin; Ding, Ke; Huang, Zhangjian; Lai, Yisheng; Peng, Sixun; Zhang, Yihua. Quality Control of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine And the article was included in European Journal of Medicinal Chemistry on April 22 ,2014. The article conveys some information:

Novel compounds were synthesized and biol. evaluated. Several ones exhibited stronger inhibitory activity than gefitinib against EGFR L858R/T790M and antiproliferative effects on H1975 and HCC827 cells. The 3-aminopropamide in some compoundslike compound I could be converted to the active acrylamide in the presence of arginine. Importantly, compound I showed improved stability relative to compound WZ4002 whose structure is same to I excepting an acrylamide moiety. Interestingly, compound II, a NO donating compound of I, showed more potent and selective inhibition than compound I on H1975 cells. Significantly, compound II produced high levels of NO in H1975 cells but not in non-tumorous 16HBE cells, and its inhibition was diminished by NO scavenger. Furthermore, compound II dose-dependently produced inhibitory effects on EGFR downstream signaling in H1975 cells. In the experiment, the researchers used 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Quality Control of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Quality Control of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amineOn November 1, 2017 ,《Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Romu, Aireen A.; Lei, Zining; Zhou, Bin; Chen, Zhe-Sheng; Korlipara, Vijaya. The article conveys some information:

A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 – 750) or Z’LYTE assay method (EGFR-WT, EGFR d746 – 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide I (R = 2′-NHCOCH2OH) exhibited complete inhibition of all the six kinases at 10 μM. Against the triple mutant, EGFR T790M C797S L858R, compounds I [R = 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH] exhibited complete inhibition at 10 μM and nearly complete inhibition at 1 μM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, I [R = 2′-N3, 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH, 4′-NHCOCH2OCH2Ph, 4′-NHCOCH2OH] were found to be the most potent compounds across all five cell lines. In the experiment, the researchers used many compounds, for example, 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Safety of 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Electric Literature of C22H25ClN6O2On November 1, 2017 ,《Design, synthesis and biological evaluation of WZ4002 analogues as EGFR inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Romu, Aireen A.; Lei, Zining; Zhou, Bin; Chen, Zhe-Sheng; Korlipara, Vijaya. The article conveys some information:

A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 – 750) or Z’LYTE assay method (EGFR-WT, EGFR d746 – 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide I (R = 2′-NHCOCH2OH) exhibited complete inhibition of all the six kinases at 10 μM. Against the triple mutant, EGFR T790M C797S L858R, compounds I [R = 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH] exhibited complete inhibition at 10 μM and nearly complete inhibition at 1 μM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, I [R = 2′-N3, 2′-NHCOCH2OCH2Ph, 2′-NHCOCH2OH, 2′-NHCO(CH2)2OCH2Ph, 2′-NHCO(CH2)2OH, 4′-NHCOCH2OCH2Ph, 4′-NHCOCH2OH] were found to be the most potent compounds across all five cell lines. In the experiment, the researchers used many compounds, for example, 4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1Electric Literature of C22H25ClN6O2)

4-(3-Aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-amine(cas: 1213269-26-1) is a member of pyrimidine. Pyrimidine derivatives are an important class of N-heterocycles. They are well-known for their wide spectrum of promising biological activities such as antitumors, bactericidals, and fungicidal.Electric Literature of C22H25ClN6O2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics