875-35-4Relevant articles and documents
Design, Synthesis, and Pharmacological Evaluation of Second Generation EZH2 Inhibitors with Long Residence Time
Apte, Shruti,Arora, Shilpi,Audia, James E.,Bradley, William D.,Brenneman, Jehrod,Bruderek, Kamil,Cantone, Nico,Cummings, Richard T.,Gehling, Victor S.,Khanna, Avinash,Levell, Julian R.,Moine, Ludivine,Ramakrishnan, Ashwin,Sims, Robert J.,Stuckey, Jacob I.,Trojer, Patrick,C?té, Alexandre
supporting information, p. 1205 - 1212 (2020/07/04)
Histone methyltransferase EZH2, which is the catalytic subunit of the PRC2 complex, catalyzes the methylation of histone H3K27 - a transcriptionally repressive post-translational modification (PTM). EZH2 is commonly mutated in hematologic malignancies and frequently overexpressed in solid tumors, where its expression level often correlates with poor prognosis. First generation EZH2 inhibitors are beginning to show clinical benefit, and we believe that a second generation EZH2 inhibitor could further build upon this foundation to fully realize the therapeutic potential of EZH2 inhibition. During our medicinal chemistry campaign, we identified 4-thiomethyl pyridone as a key modification that led to significantly increased potency and prolonged residence time. Leveraging this finding, we optimized a series of EZH2 inhibitors, with enhanced antitumor activity and improved physiochemical properties, which have the potential to expand the clinical use of EZH2 inhibition.
Preparation method for nevirapine intermediate
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Paragraph 0011; 0033; 0043; 0053; 0059; 0062-0063, (2019/01/14)
The invention provides a preparation method for a nevirapine intermediate. The preparation method comprises: performing a cyclization reaction of ammonia water, methyl cyanoacetate and methyl acetoacetate to form a compound hydroxyl: 2,6-dihydroxy-3-cyano-4-methylpyridine; adding triethylamine dropwise, introducing chlorine gas at the temperature until the reaction is complete, and obtaining 2,6-dichloro-3-cyano-4-methylpyridine; adding concentrated sulfuric acid, heating to 120 DEG C to react for 3-5 h, and then cooling to 60 DEG C; adding water to perform hydrolysis reaction, and obtaining 2,6-dichloro-3-amido-4-methylpyridine; adding a degradation reagent sodium hypochlorite, and obtaining a nevirapine intermediate 2,6-dichloro-3-amino-4- methylpyridine by Hofmann reaction. According tothe preparation method, commonly used phosphorus oxychloride is replaced with the directly introduced chlorine gas, which solves the problems that the wastewater content is too high, it is difficultto perform treatment and the odor of phosphorus oxychloride is bad, and the one-time yield of the product is 90.1%.
Wnt SIGNALING INHIBITOR, COMPOSITION, AND COMPOUND AS USE THEREFOR
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Paragraph 0079; 0080, (2017/08/15)
PROBLEM TO BE SOLVED: To provide an inhibitor for Wnt signaling route. SOLUTION: The present invention provides a compound represented by formula I, and a composition comprising the compound (X1-X8 independently represent CR4 or N; Y1 is H or C (R4)3; Y2 and Y3 independently represent H, halogen or C (R3)3; R1 and R2 independently represent H, halogen, C1-6 alkyl, quinolinyl or the like; R3s independently represent H, halogen, cyano, C1-6 alkyl or the like; R4s independently represent H, halogen, cyano, C1-6 alkoxy or the like). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT