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

• Published in: Bioorganic & medicinal chemistry letters 1998-09, Vol.8 (18), p.2467-2472
• Main Authors: Nerenberg, Jennie B., Erb, Jill M., Thompson, Wayne J., Lee, Hee-Yoon, Guare, James P., Munson, Peter M., Bergman, Jeffrey M., Huff, Joel R., Broten, Theodore P., Chang, Raymond S.L., Chen, Tsing B., O'Malley, Stacey, Schorn, Terry W., Scott, Ann L.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Urinary system
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00446-6

Benign prostatic hyperplasia can be managed pharmacologically with α-1 adrenergic receptor antagonists. Agents that demonstrate selectivity for the α-1 a 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 α-1 a adrenergic receptor antagonists which demonstrate potent effects on prostate function in vivo and are devoid of blood pressure side effects. Benign prostatic hyperplasia has been managed pharmacologically by the administration of α-1 receptor antagonists. Agents that demonstrate selectivity for the α-1a receptor subtype may offer an advantage over current therapy with respect to reducing cardiovascular side effects. Compounds reported here represent a new class of α-1a selective adrenergic antagonists.