Synthesis of some novel potent and selective catechol O-methyltransferase inhibitors.
A series of disubstituted catechol derivatives was synthesized and tested as potential COMT inhibitors. The most active compounds were more than 1000 times more potent (IC50 = 3-6 nM) in vitro than the known COMT inhibitor, 3',4'-dihydroxy-2-methylpropiophenone (U 0521, IC50 = 6000 nM). The new compounds were also highly selective COMT inhibitors with no activity against other essential enzymes involved in the synthesis and metabolism of catecholamines.
Bäckström
R
R
Orion Corporation Ltd., Orion Pharmaceutica, Research Laboratories, Espoo, Finland.
Honkanen
E
E
Pippuri
A
A
Kairisalo
P
P
Pystynen
J
J
Heinola
K
K
Nissinen
E
E
Linden
I B
IB
Männistö
P T
PT
Kaakkola
S
S
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols