943914-47-4Relevant academic research and scientific papers
Enaminone amides as novel orally active GABAA receptor modulators
Hogenkamp, Derk J.,Johnstone, Timothy B. C.,Huang, Jin-Cheng,Li, Wen-Yen,Tran, Minhtam,Whittemore, Edward R.,Bagnera, Rudy E.,Gee, Kelvin W.
, p. 3369 - 3379 (2008/02/09)
A series of enaminone esters and amides have been developed as potent allosteric modulators of γ-aminobutyric acidA (GABA A) receptors. The compounds bind to a novel modulatory site that is independent of the benzodiazepine (BZ), isosteric GABA, and neuroactive steroid binding sites. Structure-activity relationship (SAR) studies resulted in the synthesis of the c-Bu amide 16h with an in vitro potency of 7 nM based on inhibition of [35S]TBPS binding. The activity of the enaminones as positive allosteric modulators was confirmed with electrophysiological measurements in oocytes expressing α1β2γ 2L GABAA receptors. The i-Pr, s-Bu, c-Pr, and c-Bu amides (16e-h) were orally active in mice with profound central nervous system depressant effects. The i-Pr amide 16e was an orally active anxiolytic in the mouse light-dark paradigm.
