1870

New Amide Derivatives of 2,2,3,3 -Tetrametylcyclopropane Carboxylic Acid

Bialer Meir, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

 Category

LifeSciences and BioTechnology   

Keywords

Tetramethylcyclopropane carboxylic acid, VPA, derivatives

Current development stage

 TRL4 - POC of candidate drug formulation is demonstrated in defined animal model

Application

  • Epilepsy is a common neurological disorder. There are more than 20 antiepileptic drugs (AED) available. However, about 30% of epileptic patients are not seizure-free with the existing AEDs.
  • Furthermore, most of the currently utilized AEDs have side effects, which are sometimes severe and, in some cases, even fatal.
  • VPA (Valproic acid) is one of the four most prescribed AEDs. It is also used for the treatment of bipolar disorders and migraine prophylaxis.  The clinical utilization of VPA is limited by different side effects with the most serious of those being teratogenicity and life- threatening hepatotoxicity

Our Innovation

A novel 2.2.3,3-tetramethylcyclopropane carboxamide derivatives compounds

  • High anticonvulsant potency
  • Better treatment of human generalized tonic-clonic seizures and myoclonic seizures

Technology

  • The 2,2,3,3-Tetramethylcyclopropane carboxylic acid is a cyclic analogue of the antiepileptic drug (AED) valproic acid (VPA)
  • The new compound derivatives were synthesized and tested in rodent models for anticonvulsant potency and AED-induced teratogenicity
  • Our finding uncovers that α-F-TMCD was the most active compound. Its anticonvulsant potency was 120 times greater in the rat subcutaneous metrazol (scMet) test than that of the most widely used antiepileptic drug VPA
  • In the anticonvulsant rat-maximal electroshock (MES) and subcutaneous metrazol (scMet) tests, α-Cl-TMCD had ED50 values of 97mg/kg and 27mg/kg, respectively,  4 times more potent than VPA in the rat MES test
  • α-methyl-TMCD, α-F-MTMCD, α-F-TMCU and α-Br-TMCD exhibited no anticonvulsant activity in the mice MES and scMet tests.

Opportunity

  • Epilepsy affects about 1% of the world’s population. This novel compound could be used for a new potent and safe antiepileptic and CNS drug.

 

Patent Status

Granted US 7,232,929

Contact for more information:

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