Abstract
The search for antiepileptic compounds with more selective activity continues to be an area of intensive investigation in medicinal chemistry. 3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives, 3a-g, potential prodrugs incorporating the neurotransmitter GABA were synthesized and studied for crossing the blood-brain barrier (BBB). Compounds were prepared from primary amines and carbon disulfide to give dithiocarbamates 2a-g which upon reaction in situ with formaldehyde provided the intermediates Ia-g. Addition of Ia-g onto GABA furnished the title compounds 3a-g. The structures were verified by spectral data and the amounts of the compounds in the brain were investigated by using HPLC. The concentration profiles of the tested compounds in mice brain were determined and the in vivo anticonvulsant activity was measured.
Keywords: GABA, antiepileptic, pro-drugs, blood brain barrier, tetrahydro-2H-1,3, 5-thiadiazine-2-thione
Medicinal Chemistry
Title: Targeting γ-Aminobutyric Acid (GABA) Carriers to the Brain: Potential Relevance as Antiepileptic Pro-Drugs
Volume: 6 Issue: 3
Author(s): Mohammad H. Semreen, Abdel-Nasser El-Shorbagi, Taleb H. Al-Tel and Izzeddin M.M. Alsalahat
Affiliation:
Keywords: GABA, antiepileptic, pro-drugs, blood brain barrier, tetrahydro-2H-1,3, 5-thiadiazine-2-thione
Abstract: The search for antiepileptic compounds with more selective activity continues to be an area of intensive investigation in medicinal chemistry. 3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives, 3a-g, potential prodrugs incorporating the neurotransmitter GABA were synthesized and studied for crossing the blood-brain barrier (BBB). Compounds were prepared from primary amines and carbon disulfide to give dithiocarbamates 2a-g which upon reaction in situ with formaldehyde provided the intermediates Ia-g. Addition of Ia-g onto GABA furnished the title compounds 3a-g. The structures were verified by spectral data and the amounts of the compounds in the brain were investigated by using HPLC. The concentration profiles of the tested compounds in mice brain were determined and the in vivo anticonvulsant activity was measured.
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Cite this article as:
Semreen H. Mohammad, El-Shorbagi Abdel-Nasser, Al-Tel H. Taleb and Alsalahat M.M. Izzeddin, Targeting γ-Aminobutyric Acid (GABA) Carriers to the Brain: Potential Relevance as Antiepileptic Pro-Drugs, Medicinal Chemistry 2010; 6 (3) . https://dx.doi.org/10.2174/1573406411006030144
DOI https://dx.doi.org/10.2174/1573406411006030144 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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