Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.
2-aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine-isosteric inhibitors. Subnanomolar inhibitors of PDE 5 with activity in in vivo models for erectile dysfunction have been identified. BAY 38-9456 (Vardenafil-hydrochloride) has been selected for clinical studies in the indication of erectile dysfunction.
Haning
Helmut
H
Department of Medicinal Chemistry, BAYER AG, Business Group Pharma, D-42096, Wuppertal, Germany. helmut.haning.b@bayer.com
Niewöhner
Ulrich
U
Schenke
Thomas
T
Es-Sayed
Mazen
M
Schmidt
Gunter
G
Lampe
Thomas
T
Bischoff
Erwin
E
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D014227:Triazines; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5