Enaminones-versatile therapeutic pharmacophores. Further advances

Enaminones, enamines of beta-dicarbonyl compounds, have been know for many years. In our initial account (Current Med. Chem. 1994, 1, 159-175), we rep orted on the anticonvulsant activity of a series of enaminones, notably met hyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate, 9a (R=CH 3, R-1=4-Cl), which, in animal tests, compared favorably to phenytoin and c arbamazepine. Since that time, further research in our laboratory and other laboratories have expanded the therapeutic potential of these compounds. I n addition to new anticonvulsant derivatives, we have uncovered a novel bra in transport mechanism for the enaminones and developed a preliminary regre ssion model for further synthetic direction. These topics will each be pres ented and elaborated.