Inhibitors of phenylethanolamine N-methyltransferase devoid of alpha2-adrenoceptor affinity.
A series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines was synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although their PNMT inhibitory potency decreased compared with corresponding 3-methyl-, 3-hydroxymethyl- or 3-unsubstituted-THIQs, some of them showed good selectivity due to their extremely low alpha(2)-adrenoceptor affinity.
Grunewald
Gary L
GL
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA. ggrunewald@ku.edu
Lu
Jian
J
Criscione
Kevin R
KR
Okoro
Cosmas O
CO
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D044005:Tetrahydroisoquinolines; D010625:Phenylethanolamine N-Methyltransferase