Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines

[Display omitted] 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 α 2-adrenoceptor. Although α 2-adrenoceptor affinity decreas...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2005-02, Vol.15 (4), p.1143-1147
Hauptverfasser:	Grunewald, Gary L., Romero, F. Anthony, Seim, Mitchell R., Criscione, Kevin R., Deupree, Jean D., Spackman, Christy C., Bylund, David B.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Binding Sites Biological and medical sciences Catecholaminergic system Enzyme inhibitors Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Epinephrine - physiology Humans Isoquinolines - chemical synthesis Isoquinolines - chemistry Isoquinolines - pharmacology Male Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Phenylethanolamine N-methyltransferase Phenylethanolamine N-Methyltransferase - antagonists & inhibitors Phenylethanolamine N-Methyltransferase - chemistry Rats Rats, Sprague-Dawley Receptors, Adrenergic, alpha-2 - chemistry Structure-Activity Relationship Structure-based design Tetrahydroisoquinoline
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Zusammenfassung:	[Display omitted] 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 α 2-adrenoceptor. Although α 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2004.12.013