Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system.
Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and improved solubility are delineated.
Hughes
Robert O
RO
Pfizer Global Research and Development, Chesterfield Parkway West, St. Louis, MO 63017, USA. robert.o.hughes@pfizer.com
Walker
John K
JK
Cubbage
Jerry W
JW
Fobian
Yvette M
YM
Rogier
D Joseph
DJ
Heasley
Steve E
SE
Blevis-Bal
Rhadika M
RM
Benson
Alan G
AG
Owen
Dafydd R
DR
Jacobsen
E Jon
EJ
Freskos
John N
JN
Molyneaux
John M
JM
Brown
David L
DL
Stallings
William C
WC
Acker
Brad A
BA
Maddux
Todd M
TM
Tollefson
Mike B
MB
Williams
Jennifer M
JM
Moon
Joseph B
JB
Mischke
Brent V
BV
Rumsey
Jeanne M
JM
Zheng
Yi
Y
Macinnes
Alan
A
Bond
Brian R
BR
Yu
Ying
Y
D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006152:Cyclic GMP / Q000737:chemistry; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy; D008861:Microsomes / Q000187:drug effects; D008956:Models, Chemical; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000631:Aminopyridines; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP