Abstract
We describe efforts to improve the pharmacokinetic profile of the aminopyridopyrazinone class of PDE5 inhibitors. These efforts led to the discovery of 3-[(trans-4-hydroxycyclohexyl)amino]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent and selective inhibitor of PDE5 with an excellent PK profile.
MeSH terms
-
Animals
-
Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
-
Cyclic Nucleotide Phosphodiesterases, Type 6 / antagonists & inhibitors
-
Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism
-
Dogs
-
Drug Discovery
-
Humans
-
Phosphodiesterase 5 Inhibitors*
-
Phosphodiesterase Inhibitors / chemical synthesis
-
Phosphodiesterase Inhibitors / chemistry*
-
Phosphodiesterase Inhibitors / pharmacokinetics
-
Protein Isoforms / antagonists & inhibitors
-
Protein Isoforms / metabolism
-
Pyrazines / chemical synthesis
-
Pyrazines / chemistry*
-
Pyrazines / pharmacokinetics
-
Pyridines / chemical synthesis
-
Pyridines / chemistry*
-
Pyridines / pharmacokinetics
-
Rats
-
Rats, Inbred SHR
-
Structure-Activity Relationship
Substances
-
Phosphodiesterase 5 Inhibitors
-
Phosphodiesterase Inhibitors
-
Protein Isoforms
-
Pyrazines
-
Pyridines
-
Cyclic Nucleotide Phosphodiesterases, Type 5
-
Cyclic Nucleotide Phosphodiesterases, Type 6