4419

New CNS-Active Carbamate Derivatives for Epilepsy

Bialer Meir, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research
Mawasi Hafiz , HUJI, School of Medicine - IMRIC
BIBI David

 

Keywords

Antiepileptic drugs, 4-Aminobenzensulfonamides. Teratogenicity. Carbonic Anhydrase Inhibition

Current development stage

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

Application

Epilepsy therapy is based on the use of antiepileptic drugs (AEDs). However, approximately 30% of patients with epilepsy are not seizure-free with the existing medications.

Furthermore, the clinical use of the existing AEDs is restricted by their side-effects, including the teratogenicity associated with valproic acid that restricts its use in women of child-bearing age.

Therefore, there is an unmet clinical need to develop new, effective AEDs.

Our Innovation

  • Novel CNS-active carbamate derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide with a broad potent antiepileptic activity
  • Better anticonvulsant activity
  • Better protective index than valproic acid (VPA)
  • Potent inhibitors of Carbonic anhydrase (CA) isoforms I, II and VII

Technology

The researchers conducted comparative analysys of the anticonvulsant activity, neurotoxicity, teratogenicity and carbonic anhydrase (CA) inhibition of 10 new carbamate derivatives of 4-aminobenzenesulfonamide possessing 6–9 carbons in the aliphatic side chain of the carbamate moieties

The teratogenicity of the most potent anticonvulsant compounds was evaluated in mice and their CA inhibition of four human-CA isoforms was tested in vitro compared to that of acetazolamide.

Three of the ten newly synthesized carbamates showed anticonvulsant activity in the maximal-electroshock (MES) and 6 Hz tests in rodents. They induced neural tube defects only at doses markedly exceeding their anticonvulsant ED50 values. 

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Fig. 1: Structures of the synthesized and tested sulfonebenzene carbamates

Opportunity

  • New potent and safe antiepileptic drugs
  • New CNS (Central Nervous System) drugs

 

 

Contact for more information:

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