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CNS-Active Analogues of Valproic acid (VPA) Derivatives for the Treatment of Neurological Disorders

Bialer Meir, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Yagen Boris, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Devor Marshall, HUJI, Faculty of Science, The Alexander Silberman Institute for Life Sciences

Valproic acid (VPA) is a first like antiepileptic and CNS drug (Epilepsy, neuropathic pain, bipolar disorders etc). Based on a series of structure pharmacokinetic - pharmacodynamic relationship studies of VPA, we developed VPA amide analogues and derivatives with improved anticonvulsant activity while avoiding its teratogenicity and hepatotoxicity. These VPA derivatives demonstrated efficacy in animal models of neuropathic pain and bipolar disorder.

A comparison of the fluorinated and non-fluorinated VPA derivatives shows that fluorination leads to chemical structures with a favorable anticonvulsant profile and greatly reduced teratogenic potency.

Therefore, the fluorinated cyclopropyl analogues of VPA amides have the potential to become a second generation of VPA and new antiepileptic and CNS drugs.

Patent Status

Granted US 8,518,979

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Shoshana Keynan
VP, Head of Business Development, Healthcare
+972-2-6586683