title: Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction.
abstract: 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.
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., PO Box 74, Chonan, Republic of Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Hojin
authors.initials: H
authors.lastname: Choi
authors.forename: Jaekwang
authors.initials: J
authors.lastname: Lee
authors.forename: In-Chang
authors.initials: IC
authors.lastname: Hwang
authors.forename: Seung Kee
authors.initials: SK
authors.lastname: Moon
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hong Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Dai Sig
authors.initials: DS
authors.lastname: Im
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Soon Kil
authors.initials: SK
authors.lastname: Ahn
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Kim
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Han
authors.forename: Jeong Hyeok
authors.initials: JH
authors.lastname: Yoon
authors.forename: Kyung Joo
authors.initials: KJ
authors.lastname: Lee
authors.forename: Nam Song
authors.initials: NS
authors.lastname: Choi
mesh_terms: 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
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines