SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction.
Development of structure-activity relationship of cyclic guanines I lead us to discovery of a potent and selective series of phosphodiesterase 5 inhibitors 52-59 (IC50=1.3-11.0 nM, PDE6/5=116-600).
Pissarnitski
Dmitri A
DA
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. dmitri.pissarnitski@spcorp.com
Asberom
Theodros
T
Boyle
Craig D
CD
Chackalamannil
Samuel
S
Chintala
Madhu
M
Clader
John W
JW
Greenlee
William J
WJ
Hu
Yueqing
Y
Kurowski
Stanley
S
Myers
Joyce
J
Palamanda
Jairam
J
Stamford
Andrew W
AW
Vemulapalli
Subbarao
S
Wang
Yuguang
Y
Wang
Peng
P
Wu
Ping
P
Xu
Ruo
R
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D016503:Drug Delivery Systems / Q000379:methods*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000201:enzymology*; D006147:Guanine / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000737:chemistry; D013329:Structure-Activity Relationship
D010726:Phosphodiesterase Inhibitors; D011083:Polycyclic Compounds; D006147:Guanine; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human