CAS: 1233339-22-4; (R)-4-(2-(1H-Indol-4-yl)-6-(1-(Methylsulfonyl)Cyclopropyl)Pyrimidin-4-yl)-3-Methylmorpholine

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(3R)-4-[2-chloro-6-(1-methanesulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine indole-4-boronic acid [2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methyl methanesulfonate 2,6-dichloropyrimidine-4-carboxylic acid methyl ester

📜2,6-二氯嘧啶-4-甲酸甲酯置于bis-Triphenylphosphine-Palladium(II) Chloride,锂硼氢,四丁基溴化铵,Sodium Carbonate,三乙胺,Sodium Hydroxide,Lithium Iodide体系中,用 四氢呋喃,1,4-二氧六环,乙二醇二甲醚,二氯甲烷,水,N,N-二甲基甲酰胺,甲苯 用作溶剂,化学反应 45.0H,反应生成4-[4-[(3R)-3-甲基-4-吗啉基]-6-[1-(甲基磺酰基)环丙基]-2-嘧啶基]-1H-吲哚
参考文献:Discovery Of 4-{4-[(3R)-3-Methylmorpholin-4-Yl]-6-[1-(Methylsulfonyl)Cyclopropyl]Pyrimidin-2-Yl}-1H-Indole (Az20): A Potent And Selective Inhibitor Of Atr Protein Kinase With Monotherapy In Vivo Antitumor Activity
标题:Discovery Of 4-{4-[(3R)-3-Methylmorpholin-4-Yl]-6-[1-(Methylsulfonyl)Cyclopropyl]Pyrimidin-2-Yl}-1H-Indole (Az20): A Potent And Selective Inhibitor Of Atr Protein Kinase With Monotherapy In Vivo Antitumor Activity
摘要:Atr Is An Attractive New Anticancer Drug Target Whose Inhibitors Have Potential As Chemo-Or Radiation Sensitizers Or As Monotherapy In Tumors Addicted To Particular Dna-Repair Pathways. We Describe The Discovery And Synthesis Of A Series Of Sulfonylmorpholinopyrimidines That Show Potent And Selective Atr Inhibition. Optimization From A High Quality Screening Hit Within Tight Sar Space Led To Compound 6 (Az20) Which Inhibits Atr Immunoprecipitated From Hela Nuclear Extracts With An Ic50 Of 5 Nm And Atr Mediated Phosphorylation Of Chk1 In Ht29 Colorectal Adenocarcinoma Tumor Cells With An Ic50 Of 50 Nm. Compound 6 Potently Inhibits The Growth Of Lovo Colorectal Adenocarcinoma Tumor Cells In Vitro And Has High Free Exposure In Mouse Following Moderate Oral Doses. At Well Tolerated Doses 6 Leads To Significant Growth Inhibition Of Lovo Xenografts Grown In Nude Mice. Compound 6 Is A Useful Compound To Explore Atr Pharmacology In Vivo.
Doi:10.1021/jm301859S