title: Furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors for treatment of erectile dysfunction.
abstract: Synthesis of furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors was reported. Their in vitro potencies in inhibiting PDE5 and selectivity in inhibiting other PDE isozymes (PDE1-4 and PDE6) were evaluated. Some of these compounds are more potent than sildenafil with better selectivity toward PDE1 and PDE6. Incorporation of solublizing groups resulted in bioavailable analogues. Selected compounds showed in vivo efficacy in anesthetized dog model for penile erection.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development L.L.C., 1000 Route 202 South, P.O. Box 300, Raritan, New Jersey 08869, USA. wjiang1@prdus.jnj.com
authors.forename: Weiqin
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Macielag
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Walsh
authors.forename: James J
authors.initials: JJ
authors.lastname: Fiordeliso
authors.forename: James C
authors.initials: JC
authors.lastname: Lanter
authors.forename: Jihua
authors.initials: J
authors.lastname: Guan
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Patricia
authors.initials: P
authors.lastname: Kraft
authors.forename: Sheela
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Craig
authors.forename: Donna
authors.initials: D
authors.lastname: Haynes-Johnson
authors.forename: T Matthew
authors.initials: TM
authors.lastname: John
authors.forename: Joanna
authors.initials: J
authors.lastname: Clancy
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D006152:Cyclic GMP / Q000096:biosynthesis; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D007172:Erectile Dysfunction / Q000188:drug therapy; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D010410:Penile Erection / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D007527:Isoenzymes; D015363:Quinolones; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; D006152:Cyclic GMP