Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy.
By use of chemical enablement and prospective design, a novel series of selective, brain penetrant PDE9A inhibitors have been identified that are capable of producing in vivo elevations of brain cGMP.
Verhoest
Patrick R
PR
Neuroscience Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA.
Proulx-Lafrance
Caroline
C
Corman
Michael
M
Chenard
Lois
L
Helal
Christopher J
CJ
Hou
Xinjun
X
Kleiman
Robin
R
Liu
Shenping
S
Marr
Eric
E
Menniti
Frank S
FS
Schmidt
Christopher J
CJ
Vanase-Frawley
Michelle
M
Schmidt
Anne W
AW
Williams
Robert D
RD
Nelson
Frederick R
FR
Fonseca
Kari R
KR
Liras
Spiros
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C116137:PDE9A protein, human; C507055:Pde9a protein, mouse; D006152:Cyclic GMP