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).
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. dmitri.pissarnitski@spcorp.com
Dmitri A
DA
Pissarnitski
Theodros
T
Asberom
Craig D
CD
Boyle
Samuel
S
Chackalamannil
Madhu
M
Chintala
John W
JW
Clader
William J
WJ
Greenlee
Yueqing
Y
Hu
Stanley
S
Kurowski
Joyce
J
Myers
Jairam
J
Palamanda
Andrew W
AW
Stamford
Subbarao
S
Vemulapalli
Yuguang
Y
Wang
Peng
P
Wang
Ping
P
Wu
Ruo
R
Xu
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