title: Synthesis of some novel potent and selective catechol O-methyltransferase inhibitors.
abstract: 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.
authors.affiliation: Orion Corporation Ltd., Orion Pharmaceutica, Research Laboratories, Espoo, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Bäckström
authors.forename: E
authors.initials: E
authors.lastname: Honkanen
authors.forename: A
authors.initials: A
authors.lastname: Pippuri
authors.forename: P
authors.initials: P
authors.lastname: Kairisalo
authors.forename: J
authors.initials: J
authors.lastname: Pystynen
authors.forename: K
authors.initials: K
authors.lastname: Heinola
authors.forename: E
authors.initials: E
authors.lastname: Nissinen
authors.forename: I B
authors.initials: IB
authors.lastname: Linden
authors.forename: P T
authors.initials: PT
authors.lastname: Männistö
authors.forename: S
authors.initials: S
authors.lastname: Kaakkola
mesh_terms: 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
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols