Bäckström R, Honkanen E, Pippuri A, Kairisalo P, Pystynen J, Heinola K, Nissinen E, Linden I B, Männistö P T, Kaakkola S
Orion Corporation Ltd., Orion Pharmaceutica, Research Laboratories, Espoo, Finland.
J Med Chem. 1989 Apr;32(4):841-6. doi: 10.1021/jm00124a017.
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.
合成了一系列二取代儿茶酚衍生物，并作为潜在的儿茶酚-O-甲基转移酶（COMT）抑制剂进行了测试。活性最强的化合物在体外的效力比已知的COMT抑制剂3'，4'-二羟基-2-甲基苯丙酮（U 0521，IC50 = 6000 nM）高1000倍以上（IC50 = 3-6 nM）。这些新化合物还是高度选择性的COMT抑制剂，对儿茶酚胺合成和代谢中涉及的其他关键酶没有活性。
