CAS: 1360883-22-2; 2-Methyl-1H-Indole-4-Carbonitrile

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321922-05-8 1541530-91-9 36798-24-0

上下游产品

4-氰基吲哚 1H-Indole-4-Carbonitrile 16136-52-0

4-溴吲哚置于1,1'-双(二苯基膦)二茂铁,Tris-(Dibenzylideneacetone)Dipalladium(0),正丁基锂,Sodium Hydride,Sodium Hydroxide体系中,用 四氢呋喃,N-甲基吡咯烷酮,乙醇,水 用作溶剂,化学反应 18.0H,反应生成4-氰基-2-甲基-1H-吲哚
参考文献:Discovery Of A First-In-Class,Potent,Selective,And Orally Bioavailable Inhibitor Of The P97 Aaa Atpase (Cb-5083)
标题:Discovery Of A First-In-Class,Potent,Selective,And Orally Bioavailable Inhibitor Of The P97 Aaa Atpase (Cb-5083)
摘要:The Aaa-Atpase P97 Plays Vital Roles In Mechanisms Of Protein Homeostasis,Including Ubiquitin Proteasome System (Ups) Mediated Protein Degradation,Endoplasmic Reticulum-Associated Degradation (Brad),And Autophagy. Herein We Describe Our Lead Optimization Efforts Focused On In Vitro Potency,Adme,And Pharmaceutical Properties That Led To The Discovery Of A Potent,Atp-Competitive,D2-Selective,And Orally Bioavailable P97 Inhibitor 71,Cb-6083. Treatment Of Tumor Cells With 71 Leads To Significant Accumulation Of Markers Associated With Inhibition Of Ups And Erad Functions,Which Induces Irresolvable Proteotoxic Stress And Cell,Death. In Tumor Bearing Mice,Oral Administration Of 71 Causes Rapid Accumulation Of Markers Of The Unfolded Protein Response (Upr) And Subsequently Induces Apoptosis Leading To Sustained Antitumor Activity In In Vivo,Xenograft Models Of Both Solid And Hematological Tumors. 71 Has Been Taken Into Phase I Clinical Trials In Patients With Multiple Myeloma And Solid Tumors.
Doi:10.1021/acs.Jmedchem.5B01346