Linked Life Data

11931617

Source:http://linkedlifedata.com/resource/pubmed/id/11931617

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-4
pubmed:abstractText
WB4101 (1)-related compounds 5-10 were synthesized, and their biological profile at alpha(1)-adrenoreceptor (AR) subtypes and 5-HT(1A) serotoninergic receptors was assessed by binding assays in Chinese hamster ovary and HeLa cell membranes expressing the human cloned receptors. Moreover, their receptor selectivity was further determined in functional experiments in isolated rat prostate (alpha(1A)), vas deferens (alpha(1A)), aorta (alpha(1D)), and spleen (alpha(1B)). In functional assays, compound 5 was the most potent at alpha(1D)-ARs with a reversed selectivity profile (alpha(1D) > alpha(1A) > alpha(1B)) relative to both prototype 1 and phendioxan (2) (alpha(1A) > alpha(1D) > alpha(1B)), whereas compound 8, bearing a carbonyl moiety at position 1, was the most potent at alpha(1A)-ARs with a selectivity profile similar to that of prototypes. The least potent of the series was the trans isomer 6, suggesting that optimum alpha(1)-AR blocking activity in this series is associated with a cis relationship between the 2-side chain and the 4-phenyl ring rather than a trans relationship as previously observed for the 2-side chain and the 3-phenyl ring in 2 and related compounds. Binding affinity results were not in complete agreement with the selectivity profiles deriving from functional experiments. Although a firm explanation was not available, neutral and negative antagonism and receptor dimerization were considered as two possibilities to account for the difference between binding and functional affinities. Finally, compound 5 was selected for a modeling study in comparison with 1, mephendioxan (3), and open phendioxan (4) to achieve information on the physicochemical interactions that account for its high affinity toward alpha(1d/D)-ARs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1633-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11931617-Adrenergic alpha-Antagonists, pubmed-meshheading:11931617-Animals, pubmed-meshheading:11931617-Aorta, Thoracic, pubmed-meshheading:11931617-CHO Cells, pubmed-meshheading:11931617-Chromans, pubmed-meshheading:11931617-Cricetinae, pubmed-meshheading:11931617-Dioxanes, pubmed-meshheading:11931617-HeLa Cells, pubmed-meshheading:11931617-Humans, pubmed-meshheading:11931617-Male, pubmed-meshheading:11931617-Models, Molecular, pubmed-meshheading:11931617-Muscle, Smooth, pubmed-meshheading:11931617-Muscle Contraction, pubmed-meshheading:11931617-Prostate, pubmed-meshheading:11931617-Radioligand Assay, pubmed-meshheading:11931617-Rats, pubmed-meshheading:11931617-Rats, Wistar, pubmed-meshheading:11931617-Receptors, Adrenergic, alpha-1, pubmed-meshheading:11931617-Receptors, Serotonin, pubmed-meshheading:11931617-Receptors, Serotonin, 5-HT1, pubmed-meshheading:11931617-Spleen, pubmed-meshheading:11931617-Structure-Activity Relationship, pubmed-meshheading:11931617-Vas Deferens
pubmed:year
2002
pubmed:articleTitle
Structure-activity relationships in 1,4-benzodioxan-related compounds. 7. Selectivity of 4-phenylchroman analogues for alpha(1)-adrenoreceptor subtypes.
pubmed:affiliation
Department of Chemical Sciences, University of Camerino, Via S. Agostino 1, 62032 Camerino (MC), Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't