CAS: 1123172-88-2; 3,5-Difluoro-4-Nitrobenzonitrile

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110301-23-0 1131580-60-3 218632-01-0

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CAS号67567-26-4 4-溴-2,6-二氟苯胺 | CAS号1123172-89-3 3,5-二氟-4-硝基苯甲醇

4-溴-2,6-二氟苯胺置于n-甲基吡咯烷酮,Sodium Perborate,溶剂黄146体系中,化学反应 27.0H,反应生成3,5-二氟-4-硝基苯腈
参考文献:Discovery Of Cyclic Sulfone Hydroxyethylamines As Potent And Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitors: Structure-Based Design And In Vivo Reduction Of Amyloid β-Peptides
标题:Discovery Of Cyclic Sulfone Hydroxyethylamines As Potent And Selective β-Site App-Cleaving Enzyme 1 (Bace1) Inhibitors: Structure-Based Design And In Vivo Reduction Of Amyloid β-Peptides
摘要:Structure-Based Design Of A Series Of Cyclic Hydroxyethylamine Bace1 Inhibitors Allowed The Rational Incorporation Of Prime-And Nonprime-Side Fragments To A Central Core Template Without Any Amide Functionality. The Core Scaffold Selection And The Structure Activity Relationship Development Were Supported By Molecular Modeling Studies And By X-Ray Analysis Of Bace1 Complexes With Various Ligands To Expedite The Optimization Of The Series. The Direct Extension From P1-Aryl-And Heteroaryl Moieties Into The S3 Binding Pocket Allowed The Enhancement Of Potency And Selectivity Over Cathepsin D. Restraining The Design And Synthesis Of Compounds To A Physicochemical Property Space Consistent With Central Nervous System Drugs Led To Inhibitors With Improved Blood Brain Barrier Permeability. Guided By Structure-Based Optimization,We Were Able To Obtain Highly Potent Compounds Such As 60P With Enzymatic And Cellular Ic50 Values Of 2 And 50 Nm,Respectively,And With >200-Fold Selectivity Over Cathepsin D. Pharmacodynamic Studies In Apps1/16 Transgenic Mice At Oral Doses Of 180 Mu Mol/kg Demonstrated Significant Reduction Of Brain A Beta Levels.
Doi:10.1021/jm300069Y