title: N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.
abstract: 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.
authors.affiliation: Discovery Chemistry and Cardiovascular Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5400, Princeton, New Jersey 08543-5400, USA. david.rotella@bms.com
authors.forename: D P
authors.initials: DP
authors.lastname: Rotella
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Krupinski
authors.forename: R
authors.initials: R
authors.lastname: Pongrac
authors.forename: L
authors.initials: L
authors.lastname: Seliger
authors.forename: D
authors.initials: D
authors.lastname: Normandin
authors.forename: J E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007172:Erectile Dysfunction / Q000188:drug therapy*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D011688:Purinones / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D000068677:Sildenafil Citrate; D013329:Structure-Activity Relationship; D013450:Sulfones
chemical_list: C461180:1-(3-(1-((4-fluorophenyl)methyl)-7,8-dihydro-8-oxo-1H-imidazo(4,5-g)quinazolin-6-yl)-4-propoxyphenyl)carboxamide; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011688:Purinones; D011799:Quinazolines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C011145:zaprinast