Design and synthesis of N-alkylated saccharins as selective alpha-1a adrenergic receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 18; pp. 2467 - 2472
• Main Authors: Nerenberg, J B, Erb, J M, Thompson, W J, Lee, H Y, Guare, J P, Munson, P M, Bergman, J M, Huff, J R, Broten, T P, Chang, R S, Chen, T B, O'Malley, S, Schorn, T W, Scott, A L
• Format: Journal Article
• Language: English
• Published: England 22.09.1998
• Subjects: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists - chemical synthesis; Adrenergic alpha-Antagonists - pharmacology; Alkylation; Animals; Aorta - drug effects; Cell Line; CHO Cells; Cricetinae; Dogs; Drug Design; Finasteride - chemistry; Finasteride - pharmacology; Humans; In Vitro Techniques; Male; Models, Chemical; Prazosin - analogs & derivatives; Prazosin - chemistry; Prazosin - pharmacology; Prostate - drug effects; Rats; Receptors, Adrenergic, alpha-1; Saccharin - analogs & derivatives; Saccharin - chemical synthesis; Saccharin - pharmacology; Structure-Activity Relationship; Sulfonamides - chemistry; Sulfonamides - pharmacology; Tamsulosin
• ISSN: 0960-894X
• DOI: 10.1016/S0960-894X(98)00446-6

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.