Inhibitors of phenylethanolamine N-methyltransferase devoid of alpha2-adrenoceptor affinity

Gary L Grunewald; Jian Lu; Kevin R Criscione; Cosmas O Okoro

doi:10.1016/j.bmcl.2005.08.033

Inhibitors of phenylethanolamine N-methyltransferase devoid of alpha2-adrenoceptor affinity

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5319-23. doi: 10.1016/j.bmcl.2005.08.033. Epub 2005 Sep 19.

Authors

Gary L Grunewald¹, Jian Lu, Kevin R Criscione, Cosmas O Okoro

Affiliation

¹ Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA. ggrunewald@ku.edu

PMID: 16169723
DOI: 10.1016/j.bmcl.2005.08.033

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Phenylethanolamine N-Methyltransferase / antagonists & inhibitors*
Receptors, Adrenergic, alpha-2 / drug effects
Tetrahydroisoquinolines / chemical synthesis
Tetrahydroisoquinolines / chemistry*
Tetrahydroisoquinolines / pharmacology*

Substances

Enzyme Inhibitors
Receptors, Adrenergic, alpha-2
Tetrahydroisoquinolines
Phenylethanolamine N-Methyltransferase

Grants and funding

HL 34193/HL/NHLBI NIH HHS/United States