CAS: 1227911-45-6; (3S,6R)-1-(6-(3-Amino-1H-Indazol-6-yl)-2-(Methylamino)Pyrimidin-4-yl)-N-Cyclohexyl-6-Methylpiperidine-3-Carboxamide

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(3S,6R)-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide Methyl 6-methylnicotinate 4,6-dichloro-N-methyl-2-pyrimidinamine methyl (3R*,6S*)-6-methylpiperidine-3-carboxylate

6-甲基烟酸甲酯置于盐酸,Platinum(Iv) Oxide,四(三苯基膦)钯,Lithium Hydroxide Monohydrate,Palladium 10% On Activated Carbon,氢气,碳酸氢钠,一水合肼,N,N-二异丙基乙胺,Methanaminium,N-[(Dimethylamino)(3H-1,2,3-Triazolo[4,5-B]Pyridin-3-Yloxy)Methylene]-N-Methyl-,Hexafluorophosphate(1-)体系中,用 1,4-二氧六环,甲醇,乙醇,二氯甲烷,水,乙酸乙酯,异丙醇 用作溶剂,100.0 °C,448.17 Kpa 条件下,反应 49.0H,反应生成Gsk2334470游离态
参考文献:Structure-Based Design Of Potent And Selective 3-Phosphoinositide-Dependent Kinase-1 (Pdk1) Inhibitors
标题:Structure-Based Design Of Potent And Selective 3-Phosphoinositide-Dependent Kinase-1 (Pdk1) Inhibitors
摘要:Phosphoinositide-Dependent Protein Kinase-1 (Pdk1) Is A Master Regulator Of The Agc Family Of Kinases And An Integral Component Of The Pi3K/akt/mtor Pathway. As This Pathway Is Among The Most Commonly Deregulated Across All Cancers,A Selective Inhibitor Of Pdki Might Have Utility As An Anticancer Agent. Herein We Describe Our Lead Optimization Of Compound 1 Toward Highly Potent And Selective Pdki Inhibitors Via A Structure-Based Design Strategy. The Most Potent And Selective Inhibitors Demonstrated Submicromolar Activity As Measured By Inhibition Of Phosphorylation Of Pdk1 Substrates As Well As Antiproliferative Activity Against A Subset Of Aml Cell Lines. In Addition,Reduction Of Phosphorylation Of Pdk1 Substrates Was Demonstrated In Vivo In Mice Bearing oc1-Aml2 Xenografts. These Observations Demonstrate The Utility Of These Molecules As Tools To Further Delineate The Biology Of Pdki And The Potential Pharmacological Uses Of A Pdk1 Inhibitor.
Doi:10.1021/jm101527U