CAS: 33097-11-9; 4,6-Dichloro-2-(Methylthio)Pyrimidine-5-Carbaldehyde

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33097-13-1 313339-35-4 959070-42-9

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CAS号1979-98-2 2-甲硫基-4,6-二羟基嘧啶 | CAS号68-12-2 N,N-二甲基甲酰胺 | CAS号91759-32-9 2-疏基-4,6-二羟基-嘧啶 | CAS号313339-35-4 4,6-二氯-2-(甲巯基)嘧... | CAS号959070-42-9 4,6-二氯-2-甲基硫基嘧啶... | CAS号33097-12-0 2-甲硫基-4,6-二氯嘧啶-5-肟 | CAS号1220517-81-6 4-氯-1-乙基-6-(甲基硫... | CAS号85426-79-5 4-氯-6-甲基硫代-1H-吡... | CAS号444605-10-1 4-氯-2-(甲基硫代)-6-... | CAS号445040-59-5 4-氯-2-甲基磺酰基-6-吡... | CAS号445040-60-8 4-chloro-2-meth... | CAS号499197-32-9 (2-methylsulfan... | CAS号5305-56-6 4-氨基-6-氯-2-甲硫基嘧...

📜4,6-二羟基-2-甲硫基嘧啶置于三氯氧磷体系中,用 N,N-二甲基甲酰胺 用作溶剂,化学反应 1.0H,以62%的收率获得2-(甲硫基)-4,6-二氯-5-嘧啶甲醛
参考文献:A Novel Pyrazolo [3,4-D] Pyrimidine,Kkc080106,Activates The Nrf2 Pathway And Protects Nigral Dopaminergic Neurons
标题:A Novel Pyrazolo [3,4-D] Pyrimidine,Kkc080106,Activates The Nrf2 Pathway And Protects Nigral Dopaminergic Neurons
摘要:The Transcription Factor Nuclear Factor-Erythroid 2-Related Factor-2 (Nrf2) Is Known To Induce Neuroprotective And Anti-Inflammatory Effects And Is Considered To Be An Excellent Molecular Target For Drugs Related To Neurodegenerative Disease Therapy. Nrf2 Activators Previously Tested In Clinical Trials Were Electrophilic,Causing Adverse Effects Due To Non-Selective And Covalent Modification Of Cellular Thiols. In Order To Circumvent This Issue,We Constructed And Screened A Chemical Library Consisting Of 241 Pyrazolo [3,4-D] Pyrimidine Derivatives And Discovered A Novel,Non-Electrophilic Compound: 1-Benzyl-6-(Methylthio)-N-(1-Phenylethyl)-1H-Pyrazolo [3,4-D] Pyrimidine-4-Amine (Kkc080106). Kkc080106 Was Able To Activate Nrf2 Signaling As It Increases The Cellular Levels Of Nrf2,Binds To The Nrf2 Inhibitor Protein Keap1,And Causes The Accumulation Of Nuclear Nrf2. We Also Observed An Increase In The Expression Levels Of Nrf2-Dependent Genes For Antioxidative/neuroprotective Enzymes In Dopaminergic Neuronal Cells. In Addition,In Lipopolysaccharide-Activated Microglia,Kkc080106 Suppressed The Generation Of The Proinflammatory Markers,Such As Il-1 Beta,Tnf-Alpha,Cyclooxygenase-2,Inducible Nitric Oxide Synthase,And Nitric Oxide,And Inhibited The Phosphorylation Of Kinases Known To Be Involved In Inflammatory Signaling,Such As I Kappa B Kinase,P38,Jnk,And Erk. As A Drug,Kkc080106 Exhibited Excellent Stability Against Plasma Enzymes And A Good Safety Profile,Evidenced By No Mortality After The Administration Of 2000 Mg/kg Body Weight,And Minimal Inhibition Of The Herg Channel Activity. Pharmacokinetic Analysis Revealed That Kkc080106 Has Good Bioavailability And Enters The Brain After Oral And Intravenous Administration,In Both Rats And Mice. In Mptp-Treated Mice That Received Kkc080106 Orally,The Compound Blocked Microglial Activation,Protected The Nigral Dopaminergic Neurons From Degeneration,And Prevented Development Of The Dopamine Deficiency-Related Motor Deficits. These Results Suggest That Kkc080106 Has Therapeutic Potential For Neurodegenerative Disorders Such As Parkinson'S Disease.
Doi:10.1016/j.Expneurol.2020.113387