Linked Life Data

7143356

Source:http://linkedlifedata.com/resource/pubmed/id/7143356

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1983-1-7
pubmed:abstractText
Some nonaromatic analogues of amphetamine and alpha-methylbenzylamine were prepared and evaluated as competitive inhibitors of norepinephrine N-methyltransferase (NMT). All of the nonaromatic analogues were significantly more active than their aromatic counterparts [Ki for amphetamine = 740 microM; Ki for 1-cyclooctyl-2-aminopropane = 86 microM]. In order to determine if the aliphatic ring of these analogues bound to the same binding site as the phenyl ring of amphetamine and alpha-methylbenzylamine, the stereoselectivity of NMT toward the different compounds was determined. Stereochemical requirements for aromatic and nonaromatic inhibitors were similar (in all cases the S isomer was more potent at inhibiting NMT). The stereochemical preference expressed for phenylethanolamine substrates and corresponding nonaromatic analogues was also found to be the same; however, as the lipophilicity of the nonaromatic ethanolamine analogues was increased, a loss in both stereoselectivity and substrate activity occurred. The results presented here are consistent with an aromatic ring binding site that is part of, or bordered by, a large hydrophobic area. The larger, more hydrophobic nonaromatic phenylethanolamine derivatives are drawn into the hydrophobic area, which reduces side-chain hydroxy interactions necessary for substrate activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1198-204
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Importance of the aromatic ring in adrenergic amines. 7. Comparison of the stereoselectivity of norepinephrine N-methyltransferase for aromatic vs. nonaromatic substrates and inhibitors.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.