{"id":10756,"date":"2022-10-28T06:38:05","date_gmt":"2022-10-27T22:38:05","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=10756"},"modified":"2022-10-28T06:38:05","modified_gmt":"2022-10-27T22:38:05","slug":"yang-tingting-team-published-research-in-european-journal-of-medicinal-chemistry-in-2022-2075-46-9","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=10756","title":{"rendered":"Yang, Tingting team published research in European Journal of Medicinal Chemistry  in 2022 | 2075-46-9"},"content":{"rendered":"<p>Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. 2075-46-9, formula is C3H3N3O2, Name is  4-Nitro-1H-pyrazole.  Pyrazoles are a class of compounds that have the ring C3N2 with adjacent nitrogen atoms.Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol. <a href=\"https:\/\/www.ambeed.com\/products\/2075-46-9.html\">Formula: C3H3N3O2<\/a>.<\/p>\n<p>Yang, Tingting;Zhang, Wenjuan;Cao, Shengjie;Sun, Shiyang;Cai, Xu;Xu, Lei;Li, Pengyun;Zheng, Zhibing;Li, Song research published \u300a Discovery of highly potent and selective EGFR<sup>T790M\/L858R<\/sup> TKIs against NSCLC based on molecular dynamic simulation\u300b, the research content is summarized as follows. 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 EGFR<sup>WT<\/sup>. 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 EGFR<sup>T790M\/L858R<\/sup> 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 EGFR<sup>T790M\/L858R<\/sup> 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 EGFR<sup>T790M\/L858R<\/sup> for further pharmacodynamic and pharmacokinetic studies, and all these studies provide important clues for the discovery of potent EGFR<sup>T790M\/L858R<\/sup> inhibitors with high selectivity.<\/p>\n<p><a href=\"https:\/\/www.ambeed.com\/products\/2075-46-9.html\">Formula: C3H3N3O2<\/a>, 4-Nitro-1H-pyrazole, also known as 4-Nitropyrazole, is a useful research compound. Its molecular formula is C3H3N3O2 and its molecular weight is 113.08 g\/mol. The purity is usually 95%.<\/p>\n<p>4-Nitropyrazole, is a building block for the synthesis of various pharmaceutical compounds, including inhibitors, and therapeutic agents. It can be used for the synthesis of highly selective, brain-penetrant aminopyrazole LRRK2 Inhibitor, as a potentially viable treatment for Parkinson&#8217;s disease., 2075-46-9.<\/p>\n<p>Referemce:<br \/><a href=\"https:\/\/en.wikipedia.org\/wiki\/Pyrazole\">Pyrazole &#8211; Wikipedia<\/a>,<br \/><a href=\"https:\/\/www.sciencedirect.com\/topics\/chemistry\/pyrazoles\">Pyrazoles &#8211; an overview | ScienceDirect Topics<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p><a href=\"https:\/\/www.ambeed.com\/products\/2075-46-9.html\">Formula: C3H3N3O2<\/a>, 4-Nitro-1H-pyrazole, also known as 4-Nitropyrazole, is a useful research compound. Its molecular formula is C3H3N3O2 and its molecular weight is 113.08 g\/mol. The purity is usually 95%.<\/p>\n<p>4-Nitropyrazole, is a building block for the synthesis of various pharmaceutical compounds, including inhibitors, and therapeutic agents. It can be used for the synthesis of highly selective, brain-penetrant aminopyrazole LRRK2 Inhibitor, as a potentially viable treatment for Parkinson&#8217;s disease., 2075-46-9.<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[152,131],"tags":[732],"class_list":["post-10756","post","type-post","status-publish","format-standard","hentry","category-2075-46-9","category-pyrazoles-derivatives","tag-m-w100-150"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Yang, Tingting team published research in European Journal of Medicinal Chemistry in 2022 | 2075-46-9 | pyrazoles-derivatives<\/title>\n<meta name=\"description\" content=\"Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. 2075-46-9, formula is C3H3N3O2, Name is 4-Nitro-1H-pyrazole. Pyrazoles are a class of compounds that have the ring C3N2 with adjacent nitrogen atoms.Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol. 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