Innovations In Clinical Neuroscience

2015 Abstracts of Poster Presentations

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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[ V O L U M E 1 2 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 5 , S U P P L E M E N T C ] Innovations in CLINICAL NEUROSCIENCE 3 CNS DRUG COMPOUNDS Synthesis of carnitine analogues for inhibition of carnitine palmitoyltransferase Presenters: Bornstein J, Garneau- Tsodikova S Affiliations: University of Michigan Life Sciences Institute Background: Type 2 diabetes (T2DM) carries a markedly elevated risk of cerebrovascular disease. Carnitine plays a key role transporting fatty acids into mitochondria for B-oxidation and decreased levels seen in T2DM are thought to contribute to development of insulin resistance via lipid accumulation in multiple tissues. Unfortunately, the structure and mechanism of carnitine palmitoyltransferase 1 (CPT1), a key enzyme involved in this process, is not well known and could provide useful information to drive future therapeutic developments. Objective: Herein describes a method to synthesize a diverse array of L-carnitine analogues for CPT1 inhibition with the goal of elucidating key CPT1 components via future structure-activity relationship and protein binding studies. Methods: A ((S) 2,30 Epoxypropyl) trimethylammonium Chloride epoxide scaffold was synthesized via dropwise addition of ((S)-3-Chloro-2- hydroxypropyl)trimethylammonium chloride to K(t-BuOH). After purification, the resulting compound was treated with acetone cyanohydrin in water to yield a DL- carnitine nitrile. The epoxide and the nitrile were then substituted with various hydrophobic and hydrophilic functional groups. Results and conclusion: Diverse L-carnitine analogues were synthesized in short synthetic steps with 93%+ yield. In vitro Protein docking and crystal studies of these compounds are currently ongoing and may identify key components of Innov Clin Neurosci. 2015;12(11–12 Suppl C):3–17 Abstracts of Poster Presentations: CNS Summit 2015 October 7–11, 2015 Boca Raton, Florida For an alphabetical index organized by poster title or author, please see page 16 of this supplement. TOPICS CNS Drug Compounds ........3 Devices.................................6 Patient Assessment, Scales, and Tools..............................7 Rater Training and Rater Assessment..........................9 Study Protocol and Trial Methodology ......................11

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