Linked Life Data

12166948

Source:http://linkedlifedata.com/resource/pubmed/id/12166948

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2002-8-8
pubmed:abstractText
We have synthesized a series of 6,7-benzomorphan derivatives and determined their ability to bind to voltage-dependent sodium channels. We have also compared the functional consequences of this blockade in vitro and in vivo. The ability of the compounds to displace [(3)H]batrachotoxin from voltage-dependent sodium channels was compared with their ability to inhibit [(3)H]glutamate release in rat brain slices and block convulsions in the maximal electroshock test in mice. We found that the hydroxyl function in the 4'-position is crucial for improving the sodium channel blocking properties. Moreover, the stereochemistry and the topology of the N-linked side chain also influence this interaction. Indeed, the affinity is improved by an aromatic substitution in the side chain. By modifying the N substituent and the substitution pattern of the hydroxyl function, we were able to discover (2R)-[2alpha,3(S),6alpha]-1,2,3,4,5,6-hexahydro-6,11,11-tri-methyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol hydrochloride. This compound was chosen as the best candidate for further pharmacological investigations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3755-64
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke.
pubmed:affiliation
Department of Medicinal Chemistry, Boehringer Ingelheim Pharma KG, 88397 Biberach an der Riss, and Corporate Development, Boehringer Ingelheim GmbH, 55216 Ingelheim am Rhein, Germany. Matthias.Grauert@bc.boehringer-ingelheim.com
pubmed:publicationType
Journal Article, In Vitro