Identification and structure-activity studies of novel ultrashort-acting benzodiazepine receptor agonists.
The synthesis and evaluation of novel ultrashort-acting benzodiazepine (USA BZD) agonists is described. A BZD scaffold was modified by incorporation of amino acids and derivatives. The propionate side chain of glutamic acid tethers an enzymatically labile functionality where the metabolite carboxylic acid displays markedly reduced BZD receptor affinity. The USA BZDs were characterized by full agonism profiles. Copyright2000 Elsevier Science Ltd.
Stafford
Jeffrey A
JA
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA.
Pacofsky
Gregory J
GJ
Cox
Richard F
RF
Cowan
Jill R
JR
Dorsey
George F
GF
Gonzales
Stephen S
SS
Jung
David K
DK
Koszalka
George W
GW
McIntyre
Maggie S
MS
Tidwell
Jeffrey H
JH
Wiard
Robert P
RP
Feldman
Paul L
PL
D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D058785:GABA-A Receptor Agonists; D006801:Humans; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D013329:Structure-Activity Relationship
D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines