title: Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines.
abstract: 3-Hydroxyethyl- and 3-hydroxypropyl-7-substituted-tetrahydroisoquinolines (9, 10, 16, and 17) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although alpha(2)-adrenoceptor affinity decreased for these compounds, selectivity was not gained over the parent 3-hydroxymethyl compounds (1, 2) due to a loss in PNMT inhibitory potency.
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: F Anthony
authors.initials: FA
authors.lastname: Romero
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Seim
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Criscione
authors.forename: Jean D
authors.initials: JD
authors.lastname: Deupree
authors.forename: Christy C
authors.initials: CC
authors.lastname: Spackman
authors.forename: David B
authors.initials: DB
authors.lastname: Bylund
mesh_terms: D000818:Animals; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004837:Epinephrine / Q000502:physiology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D018341:Receptors, Adrenergic, alpha-2; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine