Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.
Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was selected for in vivo evaluation of lipolysis induction, metabolic rate increase, and cardiovascular effects.
Edmondson
Scott D
SD
Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
Mastracchio
Anthony
A
He
Jiafang
J
Chung
Christine C
CC
Forrest
Michael J
MJ
Hofsess
Scott
S
MacIntyre
Euan
E
Metzger
Joseph
J
O'Connor
Naphtali
N
Patel
Kajal
K
Tong
Xinchun
X
Tota
Michael R
MR
Van der Ploeg
Lex H T
LH
Varnerin
Jeff P
JP
Fisher
Michael H
MH
Wyvratt
Matthew J
MJ
Weber
Ann E
AE
Parmee
Emma R
ER
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D015195:Drug Design; D007700:Kinetics; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D014753:Vinyl Compounds; C062482:pyridazine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3