2-substituted-2-acetamido- N-benzylacetamides : synthesis, spectroscopic and anticonvulsant properties

Select functionalized amino acid derivatives of the potent anticonvulsant agent [alpha]-acetamido-H-benzylphenylacetamide (68b) and 2-acetamido-H-benzylpropionamide (68a) have been prepared and evaluated. Attention has been focused on the replacement of the [alpha]-phenyl and [alpha]-methyl groups in 68a and 68b by five-membered ring hetereoaromatic moieties, benzo-fused heteroaromatic groups, and simple polar substituents. The synthetic and pharmacological studies revealed several notable findings. First, the use of amidoalkylation procedures using boron trifluoride etherate provided a straightforward and reliable method to introduce an electron-rich heteroaromatic substituent at the a-carbon in the amino acid derivatives. This technology permitted the incorporation of acid sensitive, unsubstituted heteroaromatic compounds (i.e., pyrrole (74). indole (72) and benzofuran (75)) within the molecule. [...]