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.
Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
Scott D
SD
Edmondson
Anthony
A
Mastracchio
Jiafang
J
He
Christine C
CC
Chung
Michael J
MJ
Forrest
Scott
S
Hofsess
Euan
E
MacIntyre
Joseph
J
Metzger
Naphtali
N
O'Connor
Kajal
K
Patel
Xinchun
X
Tong
Michael R
MR
Tota
Lex H T
LH
Van der Ploeg
Jeff P
JP
Varnerin
Michael H
MH
Fisher
Matthew J
MJ
Wyvratt
Ann E
AE
Weber
Emma R
ER
Parmee
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