Probes of the active site of norepinephrine N-methyltransferase: effect of hydrophobic and hydrophilic interactions on side-chain binding of amphetamine and .alpha.-methylbenzylamine
- 1 October 1982
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 25 (10) , 1248-1250
- https://doi.org/10.1021/jm00352a031
Abstract
A series of .omega.-substituted analogs of amphetamine and .alpha.-methylbenzylamine were prepared and evaluated as inhibitors of norepinephrine N-methyltransferase (NMT). These included several alkyl side chain extended analogs as well as the terminally hydroxylated derivatives phenylalanol (6a) and phenylglycinol (7a). None of the alkyl-substituted derivatives displayed appreciable activity as inhibitors; however, the hydroxylated analogs were up to 2-fold more potent than the parent compounds. The positive contribution of the side-chain hydroxy suggests that the terminal methyl group of the lead compounds is situated close to a hydrophilic area or hydrogen bonding fnctional group within the active site.This publication has 8 references indexed in Scilit:
- Purification and Properties of Phenylethanolamine-N-methyl TransferasePublished by Elsevier ,2021
- Importance of the aromatic ring in adrenergic amines. 8. 2-(Aminomethyl)-trans-2-decalols as inhibitors of norepinephrine N-methyltransferaseJournal of Medicinal Chemistry, 1982
- Directional probes of the hydrophobic component of the aromatic ring binding site of norepinephrine N-methyltransferaseJournal of Medicinal Chemistry, 1982
- Importance of the aromatic ring in adrenergic amines. 7. Comparison of the stereoselectivity of norepinephrine N-methyltransferase for aromatics. Nonaromatic substrates and inhibitorsJournal of Medicinal Chemistry, 1982
- Importance of the aromatic ring in adrenergic amines. 6. Nonaromatic analogs of phenylethanolamine as inhibitors of phenylethanolamine N-methyltransferase: role of .pi.-electronic and steric interactionsJournal of Medicinal Chemistry, 1981
- CONFORMATIONAL PREFERENCES OF AMPHETAMINE ANALOGS FOR INHIBITION OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE - CONFORMATIONALLY DEFINED ADRENERGIC AGENTS .5.1981
- Importance of the aromatic ring in adrenergic amines. 5. Nonaromatic analogs of phenylethanolamine as inhibitors of phenylethanolamine N-methyltransferase: role of hydrophobic and steric interactionsJournal of Medicinal Chemistry, 1981
- Morphine-like properties of diphenylethylamine and related compoundsProceedings of the Royal Society of London. B. Biological Sciences, 1944