CAS: 1337532-29-2; 1-(5-(4-Amino-7-Methyl-7H-Pyrrolo[2,3-D]Pyrimidin-5-yl)-4-Fluoroindolin-1-yl)-2-(6-Methylpyridin-2-yl)Ethanone

上下游产品

2,3-dihydro-4-fluoro-1H-indole 4-fluoroindole 1,1-dimethylethyl 4-fluoro-2,3-dihydro-1H-indole-1-carboxylate 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate

📜4-氟吲哚置于盐酸,4-二甲氨基吡啶,Potassium Phosphate,Tris-(Dibenzylideneacetone)Dipalladium(0),N-溴代丁二酰亚胺(Nbs),1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物,Tri-Tert-Butylphosphonium Tetrafluoroborate,Potassium Acetate,Sodium Cyanoborohydride,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,二氯甲烷,氯仿,水,溶剂黄146,N,N-二甲基甲酰胺 用作溶剂,化学反应 104.17H,反应生成5-[4-氟-1-[(6-甲基-2-吡啶基)乙酰基]-2,3-二氢-1H-吲哚-5-基]-7-甲基-7H-吡咯并[2,3-D]嘧啶-4-胺
参考文献:Discovery Of Gsk2656157: An Optimized Perk Inhibitor Selected For Preclinical Development
标题:Discovery Of Gsk2656157: An Optimized Perk Inhibitor Selected For Preclinical Development
摘要:We Recently Reported The Discovery Of Gsk2606414 (1),A Selective First In Class Inhibitor Of Protein Kinase R (Pkr)-Like Endoplasrnic Reticulum Kinase (Perk),Which Inhibited Perk Activation In Cells And Demonstrated Tumor Growth Inhibition In A Human Tumor Xenograft In Mice. In Continuation Of Our Drug Discovery Program,We Applied A Strategy To Decrease Inhibitor Lipophilicity As A Means To Improve Physical Properties And Pharmacokinetics. This Report Describes Our Medicinal Chemistry Optimization Culminating In The Discovery Of The Perk Inhibitor Gsk2656157 (6),Which Was Selected For Advancement To Preclinical Development.
Doi:10.1021/ml400228E

专利信息

专利号:US-12427148-B2
优先权日:2018-04-28
标 题:Cancer treatment targeted to tumor adaptive responses to protein synthesis stress
发明人：RUGGERO DAVIDE; NGUYEN HAO; CARROLL PETER; CONN CRYSTAL
权利人:UNIV CALIFORNIA
摘要:In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2α axis of the UPR adaptive response. Agents that disrupt PERK-eIF2α pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.