College of Pharmacy Faculty Research ​and Publications

The Essentiality of the Vinyl Proton in Anticonvulsant Enaminones

Document Type

Article

Publication Title

Journal of the Arkansas Academy of Science

Publication Date

Spring 2020

Volume

73

Issue

1

First Page

21

Last Page

30

Abstract

Enaminones are chemical compounds consisting of an amino group linked through a C=C bond to a keto group. Enaminones analogs and have been extensively studied in anticonvulsant therapy. They appear to act through two mechanisms, (a) inhibition of the sodium channel or (b) via a GABAergic pathway. A small library of 2, 5- dimethyl enaminone derivatives were synthesized and evaluated in a series of acute preclinical seizure models to answer several questions: 1) is the vinyl proton essential for anticonvulsant activity, 2) why is the vinyl proton required for activity, and 3) can we substitute any further? Most of the compounds showed protection against MES, scPTZ and/or 6 Hz-induced seizures. Three compounds (5i, 5l, 5p) emerged with activity at 100 and 300mg/kg and no toxicity in MES studies.

Copyright held by

Henry North

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