Linked Life Data

3037081

Source:http://linkedlifedata.com/resource/pubmed/id/3037081

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1987-8-7
pubmed:abstractText
Hybrid molecules incorporating pharmacologically important structural features of both 3-carboxy-beta-carbolines and 1,4-benzodiazepines were synthesized, and their affinities for the benzodiazepine receptor were determined in vitro. One of these hybrids, 8,14-dioxo-13,14-dihydro-8H-indolo[3',2':4,5]pyrido[2,1-c] [1,4]benzodiazepine (13), demonstrated high affinity for the receptor, displacing both benzodiazepines (IC50 = 23 nM) and beta-carbolines (IC50 = 47 nM) from their binding sites. Of the compounds synthesized, 13 also most closely satisfied the structural requirements that generally ensure a high affinity of both beta-carbolines and benzodiazepines for the receptor (e.g., aromaticity of the beta-carboline, presence of a carbonyl at C-3 of the beta-carboline and of a pi 2-region on the benzodiazepine). The hybrids not fulfilling these requirements had no affinity for the receptor. In vivo pharmacological properties of 13 could not be demonstrated because of its metabolic instability and/or its poor transport into the brain. The results are discussed in terms of a possible overlapping of beta-carboline binding sites with those of benzodiazepines on the receptor.
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:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1248-54
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Synthesis of beta-carboline-benzodiazepine hybrid molecules: use of the known structural requirements for benzodiazepine and beta-carboline binding in designing a novel, high-affinity ligand for the benzodiazepine receptor.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't