Linked Life Data

8093737

Source:http://linkedlifedata.com/resource/pubmed/id/8093737

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-2-19
pubmed:abstractText
Analogs of N,N'-bis[6-[(2-methoxybenzyl)amino]hex-1-yl]cystamine (benextramine, BXT, 2) were synthesized using solution-phase peptide synthesis methodology and analyzed for activity in displacing specifically bound 1 nM N-[propionyl-3H]neuropeptide Y([3H]NPY) from benextramine-sensitive neuropeptide Y (NPY) binding sites in rat brain. Our new synthetic approach to these analogs began with the acylation of cystamine with the N-hydroxysuccinimide ester of tert-butyloxycarbonyl (t-Boc) protected 6-aminohexanoic acid, followed by deprotection of the t-Boc groups with 4 N HCl in dioxane. Acylation of this symmetric diamine with N-hydroxysuccinimide esters of appropriately substituted benzoic acids, followed by reduction of the resultant tetraamides with diborane in refluxing THF, afforded the target compounds. The BXT analog lacking the benzylic group (i.e., compound 11) had no [3H]NPY displacement activity at concentrations up to 1.4 x 10(-3) M. The 9-fold range in activities observed for the ortho, meta, and para regioisomers of the methoxy, chloro, and hydroxy benextramine analogs at benextramine-sensitive NPY rat brain binding sites does not differ from the range of potencies observed at alpha-adrenoceptors. However, the order of potencies at [3H]NPY sites differs from the order of potencies at alpha-adrenoceptors, with the m-methoxyphenyl (9a), m-hydroxyphenyl (10b), and 2-naphthyl (9f) analogs being the most active at [3H]NPY binding sites. The present results demonstrate the importance of the benzylic moiety for BXT's NPY antagonist activity, and suggest that the BXT binding site on the NPY receptor is significantly distinct from that on the alpha-adrenoceptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
272-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Benextramine-neuropeptide Y receptor interactions: contribution of the benzylic moieties to [3H]neuropeptide Y displacement activity.
pubmed:affiliation
Department of Medicinal Chemistry, School of Pharmacy, University of Kansas, Lawrence 66045-2506.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't