Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors.
Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds. In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones were also shown to be potent and selective PDE inhibitor scaffolds with in vivo activity. SAR trends were elucidated for sulfonamide derivatives with generality across different scaffolds.
Haning
Helmut
H
BAYER HealthCare AG, Business Group Pharma, D-42096 Wuppertal, Germany. helmut.Haning@bayerhealthcare.com
Niewöhner
Ulrich
U
Schenke
Thomas
T
Lampe
Thomas
T
Hillisch
Alexander
A
Bischoff
Erwin
E
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D006571:Heterocyclic Compounds; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5