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参考文献:Synthesis And Biological Evaluation Of Cyclic Analogs Of L-Carnitine As Potential Agents In The Treatment Of Myocardial Ischemia
标题:Synthesis And Biological Evaluation Of Cyclic Analogs Of L-Carnitine As Potential Agents In The Treatment Of Myocardial Ischemia
摘要:A Series Of Cyclic Rigid Analogues Of L-Carnitine Has Been Synthesized And Examined For Activity As Substrates For The Carnitine-Acylcarnitine Translocase,The Enzyme That Mediates Transport Of Fatty Acids Into The Mitochondria. Synthetic Steps To Seven Of These Analogues Are Described In This Paper. Bioassay Of These Compounds Is Conducted In A Preparation Of Isolated Heart Mitochondria That Have Been Previously Loaded With [14C]-L-Carnitine. Efflux Of Radioactivity From The Mitochondria Is Then Monitored In The Presence Of The Compound Being Evaluated In Order To Assess The Amount Of Enzyme Activity Initiated. The Palmityl Ester Of L-N,N-Dimethyl-Trans-2-Carboxy-4-Hydroxypyrrolidinium Chloride Elicited A 13.63 And 63.07% Efflux Of [14C]-L-Carnitine At Concentrations Of 3 And 50 Mm,Respectively. This Represents The First Instance In Which A Nonnaturally occurring Analogue Of L-Carnitine Has Been Shown To Undergo Transport Via This Mitochondrial Translocase,Suggesting The Possibility That Cyclic Carnitine Analogues May Find Utility As Agents In The Treatment Of Myocardial Ischemia.
DOI:10.1021/jm00155A045