Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists.
The ultrashort-acting benzodiazepine (USA BZD) agonists reported previously have been structurally modified to improve aqueous solubility. Lactam-to-amidine modifications, replacement of the C5-haloaryl ring, and annulation of heterocycles are presented. These analogues retain BZD receptor potency and full agonism profiles.
Pacofsky
Gregory J
GJ
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA.
Stafford
Jeffrey A
JA
Cox
Richard F
RF
Cowan
Jill R
JR
Dorsey
George F
GF
Gonzales
Stephen S
SS
Kaldor
Istvan
I
Koszalka
George W
GW
Lovell
George G
GG
McIntyre
Maggie S
MS
Tidwell
Jeffrey H
JH
Todd
Dan
D
Whitesell
Graham
G
Wiard
Robert P
RP
Feldman
Paul L
PL
D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015195:Drug Design; D058785:GABA-A Receptor Agonists; D007202:Indicators and Reagents; D008968:Molecular Conformation; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship
D058785:GABA-A Receptor Agonists; D007202:Indicators and Reagents; D001569:Benzodiazepines