New CNS-Active Carbamate Derivatives for Epilepsy
New CNS-active carbamate derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide with a broad potent antiepileptic activity Project ID : 6-2017-4419
Summary of the technology
New CNS-active carbamate derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide with a broad potent antiepileptic activity
Project ID : 6-2017-4419
Description of the technology
Antiepileptic drugs, 4-Aminobenzensulfonamides. Teratogenicity. Carbonic Anhydrase Inhibition
Current development stage
TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model
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.
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.
Fig. 1: Structures of the synthesized and tested sulfonebenzene carbamates