CAS: 1003712-18-2; 2,3-Difluoro-5-Methylbenzonitrile

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1003709-96-3 508203-48-3 21524-39-0

上下游产品

1,2-difluoro-3-iodo-5-methylbenzene 3,4-difluorotoluene

3,4-二氟甲苯置于正丁基锂,Copper(L) Cyanide体系中,用 四氢呋喃,甲基叔丁基醚,N,N-二甲基甲酰胺 用作溶剂,化学反应 23.0H,反应生成2,3-二氟-5-甲基苯腈
参考文献:Discovery,Mechanism And Metabolism Studies Of 2,3-Difluorophenyl-Linker-Containing Parp1 Inhibitors With Enhanced In Vivo Efficacy For Cancer Therapy
标题:Discovery,Mechanism And Metabolism Studies Of 2,3-Difluorophenyl-Linker-Containing Parp1 Inhibitors With Enhanced In Vivo Efficacy For Cancer Therapy
摘要:Poly (Adp-Ribose) Polymerase 1 (Parp1) Is Overexpressed In A Variety Of Cancers,Especially Breast And Ovarian Cancers,And Tumor Cell Lines Deficient In Breast Cancer Gene 1/2 (Brca1/2) Are Highly Sensitive To Parp1 Inhibition. In This Study,With The Help Of Molecular Docking,We Identified A Novel Series Of 2,3-Difluorophenyl-Linker Analogues (15-54) Derived From Olaparib (1) As Parpi Inhibitors. Lead Optimization Led To The Identification Of 47,Which Showed High Selectivity And High Potency Against Parp1 Enzyme (Ic50 = 13 Nm),V-C8 Cells (Ic50 = 0.003 Nm),Capan-1 Cells (Ic50 = 7.1 Nm) And Mda-Mb-436 Cells (Ic50 = 0.2 Nm). Compound 47 Had More Potent Parpi-Dna Trapping And Double-Strand Breaks (Dsbs)-Induction Activities Than 1 And Induced G2/m Arrest And Caspase-Dependent Apoptosis. Compound 47 (50 Mg/kg,94.2%) Had A More Beneficial Effect On Tumor Growth Inhibition Than 1 (100 Mg/kg,65.0%) In A Brca1-Mutated Xenograft Model And Significantly Inhibited Tumor Growth (40 Mg/kg,48.1%) In A Brca2-Mutated Xenograft Model,With No Negative Influence On The Body Weight Of The Mice. Collectively,These Data Demonstrated That 47 Might Be An Excellent Drug Candidate For The Treatment Of Cancer,Especially For Brca-Deficient Tumors. (C) 2017 Elsevier Masson Sas. All Rights Reserved.
Doi:10.1016/j.Ejmech.2017.06.053