title: Design and synthesis of N-alkylated saccharins as selective alpha-1a adrenergic receptor antagonists.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co., West Point, PA 19486, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Nerenberg
authors.forename: J M
authors.initials: JM
authors.lastname: Erb
authors.forename: W J
authors.initials: WJ
authors.lastname: Thompson
authors.forename: H Y
authors.initials: HY
authors.lastname: Lee
authors.forename: J P
authors.initials: JP
authors.lastname: Guare
authors.forename: P M
authors.initials: PM
authors.lastname: Munson
authors.forename: J M
authors.initials: JM
authors.lastname: Bergman
authors.forename: J R
authors.initials: JR
authors.lastname: Huff
authors.forename: T P
authors.initials: TP
authors.lastname: Broten
authors.forename: R S
authors.initials: RS
authors.lastname: Chang
authors.forename: T B
authors.initials: TB
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: O'Malley
authors.forename: T W
authors.initials: TW
authors.lastname: Schorn
authors.forename: A L
authors.initials: AL
authors.lastname: Scott
mesh_terms: 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
chemical_list: 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