CAS: 1220418-77-8; Methyl 6-Bromoquinoline-3-Carboxylate

相似化合物

798545-30-9 1196155-68-6 1001756-23-5

上下游产品

methyl 3,3-dimethoxypropionate 2-amino-5-bromobenzaldehyde 5-bromo-2-aminobenzoic acid methyl ester methanol 6-bromoquinoline-3-carbaldehyde

📜5-溴氨基苯甲酸甲酯置于lithium Aluminium Tetrahydride,对甲苯磺酸体系中,用 四氢呋喃,甲苯 用作溶剂,化学反应 1.5H,反应生成6-溴喹啉-3-羧酸甲酯
参考文献:From Fragment Screening To In Vivo Efficacy: Optimization Of A Series Of 2-Aminoquinolines As Potent Inhibitors Of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (Bace1)
标题:From Fragment Screening To In Vivo Efficacy: Optimization Of A Series Of 2-Aminoquinolines As Potent Inhibitors Of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (Bace1)
摘要:Using Fragment-Based Screening Of A Focused Fragment Library,2-Aminoquinoline I Was Identified As An Initial Hit For Bace1. Further Sar Development Was Supported By X-Ray Structures Of Bace1 Cocrystallized With Various Ligands And Molecular Modeling Studies To Expedite The Discovery Of Potent Compounds. These Strategies Enabled Us To Integrate The C-3 Side Chain On 2-Aminoquinoline 1 Extending Deep Into The P2' Binding Pocket Of Bace1 And Enhancing The Ligand'S Potency. We Were Able To Improve The Bace1 Potency To Subnanomolar Range,Over 10(6)-Fold More Potent Than The Initial Hit (900 Mu M). Further Elaboration Of The Physical Properties Of The Lead Compounds To Those More Consistent With Good Blood-Brain Barrier Permeability Led To Inhibitors With Greatly Improved Cellular Activity And Permeability. Compound 59 Showed An Ic50 Value Of 11 Nm On Bace1 And Cellular Activity Of 80 Nm,This Compound Was Advanced Into Rat Pharmacokinetic And Pharmacodynamic Studies And Demonstrated Significant Reduction Of A Beta Levels In Cerebrospinal Fluid (Csf).
Doi:10.1021/jm200544Q