364

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

Category

Chemistry & Materials   

Keywords

VPA, Epilepsy, Neuropathic Pain and Bipolar Disorder

Current development stage

TRL 4, POC demonstrated, anticonvulsant activity tested in animal models

Application

  • Prolonged epileptic seizures may lead to the development of life threatening cerebral state of a persistent seizure, referred as Status epilepticus (SE). Oral administration of anti-convulsants antiepileptic drugs (AEDs) as well as brain surgery for some cases are two major types of treatments for epileptic patients.
  • Valproic acid (VPA) is a broad spectrum and antiepileptic and CNS-active agent used as an anticonvulsant and mood-stabilizing drug in the treatment of epilepsy and CNS related conditions.  Extensive efforts have been directed towards therapeutically active derivatives of VPA which exhibit to improve their activity and reduce side effects.
  • 2,2,3,3-tetramethylcyclopropane carboxamides were found promising to be novel derivatives of cyclopropyl carboxy compounds, to overcome limitations of VPA existing agents.

Our Innovation

The researchers developed novel classes and preparation process of α -Substituted cyclo propylcarboxy compounds, and specifically, novel α -halo- and α -alkyl-substituted cyclopropylcarboxy compounds.

The pharmaceutical composition may be formulated for multiple routes of administration such as topical, oral, inhalation, or parenteral.

Technology

The researchers developed procedures for synthetic pathways for preparation of panecarboxylic acids and related compounds.

  •  α-halo-2,2,3,3-tetramethylcyclopro panecarboxylic acid (α-halo-TCMA)
  • α-bromo-2,2,3,3-tetramethylcyclopro panecarboxylic acid (α -bromo-TMCA)
  • α-chloro-2,2,3,3-tetramethylcyclopro panecarboxylic acid (α -chloro-TMCA)
  • α-fluoro-2,2,3,3-tetramethylcyclopro panecarboxylic acid (α -fluoro-TMCA)

Opportunity

In a search for a potent yet safer AEDs, having none or milder adverse side effects, the present inventors have designed a novel, unexplored path by preparing a series of derivatives of cyclopropylcarboxy compounds, which include a substituent at the α -position of the cyclopropane ring.

Various features of the invention may also be provided separately or in any suitable subcombination.

 

Patent Status

Granted US 8,518,979

Contact for more information:

Mel Larrosa
VP Business Development Healthcare
+972-2-6586692