title: Inhibitors of phenylethanolamine N-methyltransferase devoid of alpha2-adrenoceptor affinity.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA. ggrunewald@ku.edu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Grunewald
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Criscione
authors.forename: Cosmas O
authors.initials: CO
authors.lastname: Okoro
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D044005:Tetrahydroisoquinolines; D010625:Phenylethanolamine N-Methyltransferase