Dihydropyrimidinone positive modulation of delta-subunit-containing gamma-aminobutyric acid type A receptors, including an epilepsy-linked mutant variant.

Gamma-aminobutyric acid type A receptors (GABA(A) receptors) are ligand-gated chloride channels that play a central role in signal transmission within the mammalian central nervous system. Compounds that modulate specific GABA(A) receptor subtypes containing the delta-subunit are scarce but would be valuable research tools and starting points for potential therapeutic agents. Here we report a class of dihydropyrimidinone (DHPM) heterocycles that preferentially potentiate peak currents of recombinant GABA(A) receptor subtypes containing the delta-subunit expressed in HEK293T cells.

Studies on the chemistry and reactivity of alpha-substituted ketones in isonitrile-based multicomponent reactions.

Using the Passerini and Ugi reactions as representative tests, the utility of several alpha-substituted ketones R-CO-CH(2)-X (X = sulfonyloxy, acyloxy, azido, halo, hydroxy, and sulfonyl) in isonitrile-based multicomponent reactions was explored. In a relative rate study (R = PhCH(2)CH(2)), each of the alpha-substituted ketones underwent Passerini condensation more rapidly than the parent ketone. Short, highly convergent routes to oxazoline, beta-lactam, di-O-acylglyceramides, and other molecular frameworks were developed.