N-3-Substituted Imidazoquinazolinones:  Potent and Selective PDE5 Inhibitors as Potential Agents for Treatment of Erectile Dysfunction

• Published in: Journal of medicinal chemistry Vol. 43; no. 7; pp. 1257 - 1263
• Main Authors: Rotella, David P, Sun, Zhong, Zhu, Yeheng, Krupinski, John, Pongrac, Ronald, Seliger, Laurie, Normandin, Diane, Macor, John E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 06-04-2000
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Animals; Biological and medical sciences; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction - drug therapy; Genital system. Reproduction; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; In Vitro Techniques; Male; Medical sciences; Penis - drug effects; Penis - physiology; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Piperazines - pharmacology; Purines; Purinones - chemistry; Quinazolines - chemical synthesis; Quinazolines - chemistry; Quinazolines - pharmacology; Rabbits; Sildenafil Citrate; Structure-Activity Relationship; Sulfones; Erection disorders; Enzyme; Nitrogen heterocycle; Lactam; Enzyme inhibitor; Esterases; Phosphoric diester hydrolases; Tricyclic compound; In vitro; Biological activity; Hydrolases; Benzamide derivatives; Carboxamide; Benzenic compound; Aromatic compound; Sildenafil; Chemical synthesis; Male genital diseases
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm000081+

Phosphodiesterase type 5 (PDE5) inhibitors with improved PDE isozyme selectivity relative to sildenafil may result in agents for the treatment of male erectile dysfunction (MED) with a lower incidence of PDE-associated adverse effects. This paper describes the discovery of 14, a PDE5 inhibitor with improved potency and selectivity in vitro compared to sildenafil. This compound shows activity in a functional assay of erectile function comparable to that of sildenafil.