Design and synthesis of N-alkylated saccharins as selective alpha-1a adrenergic receptor antagonists.
Benign prostatic hyperplasia can be managed pharmacologically with alpha-1 adrenergic receptor antagonists. Agents that demonstrate selectivity for the alpha-1a receptor subtype may offer advantages in clinical applications with respect to hypotensive side effects. The N-alkylated saccharins reported here represent a new class of subtype selective alpha-1a adrenergic receptor antagonists which demonstrate potent effects on prostate function in vivo and are devoid of blood pressure side effects.
Nerenberg
J B
JB
Department of Medicinal Chemistry, Merck & Co., West Point, PA 19486, USA.
Erb
J M
JM
Thompson
W J
WJ
Lee
H Y
HY
Guare
J P
JP
Munson
P M
PM
Bergman
J M
JM
Huff
J R
JR
Broten
T P
TP
Chang
R S
RS
Chen
T B
TB
O'Malley
S
S
Schorn
T W
TW
Scott
A L
AL
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000478:Alkylation; D000818:Animals; D001011:Aorta / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D015195:Drug Design; D018120:Finasteride / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008956:Models, Chemical; D011224:Prazosin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1; D012439:Saccharin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D000077409:Tamsulosin
C547713:ADRA1A protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D018120:Finasteride; C041226:Terazosin; D012439:Saccharin; D000077409:Tamsulosin; D011224:Prazosin