CAS: 1337531-36-8; 1-(5-(4-Amino-7-Methyl-7H-Pyrrolo[2,3-D]Pyrimidin-5-yl)Indolin-1-yl)-2-(3-(Trifluoromethyl)Phenyl)Ethanone

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5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydr°Chloride 3-(trifluoromethyl)phenylacetic acid 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 4-chloro-1H-pyrrolo[2,3-d]pyrimidine

📜N-Boc-5-溴吲哚啉置于盐酸,Tris(Dibenzylideneacetone)Dipalladium(0) Chloroform Complex,1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物,Potassium Phosphate Monohydrate,Potassium Acetate,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-),Tri Tert-Butylphosphoniumtetrafluoroborate体系中,用 1,4-二氧六环,乙醇,水,N,N-二甲基甲酰胺 用作溶剂,化学反应 29.0H,反应生成7-甲基-5-[1-[[3-(三氟甲基)苯基]乙酰基]-2,3-二氢-1H-吲哚-5-基]-7H-吡咯并[2,3-D]嘧啶-4-胺
参考文献:Discovery Of 7-Methyl-5-(1-{[3-(Trifluoromethyl)Phenyl]Acetyl}-2,3-Dihydro-1H-Indol-5-yl)-7H-Pyrrolo[2,3-D]Pyrimidin-4-Amine (Gsk2606414),A Potent And Selective First-In-Class Inhibitor Of Protein Kinase R (Pkr)-Like Endoplasmic Reticulum Kinase (Perk)
标题:Discovery Of 7-Methyl-5-(1-{[3-(Trifluoromethyl)Phenyl]Acetyl}-2,3-Dihydro-1H-Indol-5-yl)-7H-Pyrrolo[2,3-D]Pyrimidin-4-Amine (Gsk2606414),A Potent And Selective First-In-Class Inhibitor Of Protein Kinase R (Pkr)-Like Endoplasmic Reticulum Kinase (Perk)
摘要:Protein Kinase R (Pkr)-Like Endoplasmic Reticulum Kinase (Perk) Is Activated In Response To A Variety Of Endoplasmic Reticulum Stresses Implicated In Numerous Disease States. Evidence That Perk Is Implicated In Tumorigenesis And Cancer Cell Survival Stimulated Our Search For Small Molecule Inhibitors. Through Screening And Lead Optimization Using The Human Perk Crystal Structure,We Discovered Compound 38 (Gsk2606414),An Orally Available,Potent,And Selective Perk Inhibitor. Compound 38 Inhibits Perk Activation In Cells And Inhibits The Growth Of A Human Tumor Xenograft In Mice.
Doi:10.1021/jm300713S

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.