Furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors for treatment of erectile dysfunction.
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.
Jiang
Weiqin
W
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
Sui
Zhihua
Z
Macielag
Mark J
MJ
Walsh
Shawn P
SP
Fiordeliso
James J
JJ
Lanter
James C
JC
Guan
Jihua
J
Qiu
Yuhong
Y
Kraft
Patricia
P
Bhattacharjee
Sheela
S
Craig
Elizabeth
E
Haynes-Johnson
Donna
D
John
T Matthew
TM
Clancy
Joanna
J
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
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