D-色氨酸甲酯置于三乙胺,三氟乙酸体系中,用 乙醇,二氯甲烷,氯仿 用作溶剂,化学反应 24.0H,反应生成氨基他达那非
参考文献:Drug To Genome To Drug: Discovery Of New Antiplasmodial Compounds
标题:Drug To Genome To Drug: Discovery Of New Antiplasmodial Compounds
摘要:The Dominant Strategy For Discovery Of New Antimalarial Drugs Relies On Cell-Free Assays On Specific Biochemical Pathways Of Plasmodium Falciparum . However,It Appears That Screening Directly On The Parasite Is A More Rewarding Approach. The "Drug To Genome To Drug" Approach Consists Of Testing A Small Set Of Structural Analogues Of A Drug Acting On Human Proteins That Have Plasmodial Orthologues. Both Man And Plasmodium Possess Cyclic Nucleotide Phosphodiesterases (Pdes) That Are Key Players Of Cell Homeostasis. We Synthesized And Tested 40 Analogues Of Tadalafil,A Human Pde5 Inhibitor,On P. Falciparum In Culture And Obtained Potent Inhibitors Of Parasite Growth. We Discuss The Structure-Activity Relationships,Which Support The Hypothesis That Our Compounds Kill The Parasite Via Inhibition Of Plasmodial Pde Activity. We Also Prove That Antiplasmodial Derivatives Inhibit The Hydrolysis Of Cyclic Nucleotides Of The Parasite,Validating The Camp/cgmp Pathways As Therapeutic Targets Against Plasmodium Falciparum .
Doi:10.1021/jm1014617