Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction.
In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure-activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described.
Kim
Young Hoon
YH
Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., PO Box 74, Chonan, Republic of Korea.
Choi
Hojin
H
Lee
Jaekwang
J
Hwang
In-Chang
IC
Moon
Seung Kee
SK
Kim
Soo Jin
SJ
Lee
Hong Woo
HW
Im
Dai Sig
DS
Lee
Sung Sook
SS
Ahn
Soon Kil
SK
Kim
Sang Woong
SW
Han
Cheol Kyu
CK
Yoon
Jeong Hyeok
JH
Lee
Kyung Joo
KJ
Choi
Nam Song
NS
D020650:Combinatorial Chemistry Techniques; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000627:therapeutic use*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines