Phenylacetamides as selective alpha-1A adrenergic receptor antagonists.
A novel class of potent and selective alpha-1a receptor antagonists has been identified. The structures of these antagonists were derived from truncating the 4-aryl dihydropyridine subunit present in known alpha-1a antagonists. The design principles which led to the discovery of substituted phenylacetamides, the synthesis and SAR of key analogues, and the results of select in vitro and in vivo studies are described.
Patane
M A
MA
Department of Medicinal Chemistry, Merck & Co., Inc., West Point, PA 19486, USA. michael_patane@merck.com
DiPardo
R M
RM
Newton
R C
RC
Price
R P
RP
Broten
T P
TP
Chang
R S
RS
Ransom
R W
RW
Di Salvo
J
J
Nagarathnam
D
D
Forray
C
C
Gluchowski
C
C
Bock
M G
MG
D000081:Acetamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D013329:Structure-Activity Relationship
D000081:Acetamides; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists