Potent and selective xanthine-based inhibitors of phosphodiesterase 5.
Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21.
Arnold
Nichola J
NJ
Novartis Institutes of Biomedical Research, Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
Arnold
Ruth
R
Beer
David
D
Bhalay
Gurdip
G
Collingwood
Stephen P
SP
Craig
Sarah
S
Devereux
Nicholas
N
Dodds
Mark
M
Dunstan
Andrew R
AR
Fairhurst
Robin A
RA
Farr
David
D
Fullerton
Joseph D
JD
Glen
Angela
A
Gomez
Sylvie
S
Haberthuer
Sandra
S
Hatto
Julia D I
JD
Howes
Colin
C
Jones
Darryl
D
Keller
Thomas H
TH
Leuenberger
Beate
B
Moser
Heinz E
HE
Muller
Irene
I
Naef
Reto
R
Nicklin
Paul A
PA
Sandham
David A
DA
Turner
Katharine L
KL
Tweed
Morris F
MF
Watson
Simon J
SJ
Zurini
Mauro
M
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D002417:Cattle; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010599:Pharmacokinetics; D020033:Protein Isoforms / Q000187:drug effects; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D014970:Xanthines; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human