Linked Life Data

7629808

Source:http://linkedlifedata.com/resource/pubmed/id/7629808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1995-9-1
pubmed:abstractText
Synthesis and pharmacological evaluation of a series of condensed quinoline derivatives bearing a basic nitrogen on piperazine or [(dimethylamino)ethyl]thio moieties attached at the 2-position of the quinoline nucleus are described. 5-HT receptor binding studies revealed, for most of the compounds studied, nanomolar affinity for the 5-HT3 receptor subtype. The most active compound, benzopyrano[3,4-c]quinoline derivative 5f, displayed a Ki value very similar to that reported for quipazine along with an improved selectivity. Functional and in vivo testing carried out on three selected compounds showed that 5f,j,n are potent 5-HT3 receptor antagonists with potencies in the same range as the best known 5-HT3 receptor antagonists ondansetron, tropisetron, and zacopride. The crystal and molecular structures of compounds 5f,j,n were determined by single-crystal X-ray diffraction and used as starting structures for molecular modeling studies. Comparative molecular field analysis (CoMFA) was applied to binding constants of compounds 5a-p and 6a-h. The cross-validated r2, derived from partial least-squares calculations, indicated a good predictive capacity for affinity values in the series of compounds investigated. Evidence for the prediction capacity is provided in the form of plots of actual vs predicted pKi values. The steric and electrostatic features of the CoMFA-derived model are presented as standard coefficient contour maps of steric and electrostatic fields.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
2692-704
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Novel, potent, and selective 5-HT3 receptor antagonists based on the arylpiperazine skeleton: synthesis, structure, biological activity, and comparative molecular field analysis studies.
pubmed:affiliation
Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Italy.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't