Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists.
We disclose a new compound class of potent and selective alpha-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are presented.
DiPardo
R M
RM
Department of Medicinal Chemistry, Merck & Co., Inc., 19486, West Point, PA, USA.
Patane
M A
MA
Newton
R C
RC
Price
R
R
Broten
T P
TP
Chang
R S
RS
Ransom
R W
RW
Di Salvo
J
J
Freidinger
R M
RM
Bock
M G
MG
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004285:Dogs; D006207:Half-Life; D007094:Imides / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
D058668:Adrenergic alpha-1 Receptor Antagonists; D007094:Imides; D010880:Piperidines