Deficiency in the neurotramiter GABA has been implicated in CNS disorders such as epilepsy, anxiety/depression, neuropathis pain, and cognitive impairment. Neurotransmission of GABA is terminated via transport by GABA transport proteins (GATs). Inhibition of GAT effectively increases the amount of GABAergic neurotransmission, which would be a amount likely therapy for the above listed CNS disorders. Currently there are four isoforms of GAT: GAT1, BGT-1, GAT2, and GAT3. These isoforms differ in their pharmacological role and location within the CNS. The FDA-approved compound tiagabine is a GAT1 inhibitor and is used as an antiepileptic drug (AED). Surprisingly there is limited knowledge as to what therapeutic significance inhibition of the other isoforms (non-GAT1) may offer due to the lack of potent and selective inhibitors of these non-GAT1 isoforms. Here in, we propose the synthesis of GABA mimics containing a cyclic sulfinimidamide- a carboxylic acid bioisostere- in hopes that these compounds will exhibit non-GAT1 activity.

Cyclic sulfinimidamides prospective use as non-GAT1 inhibitors

249th National Meeting (2015)

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