Linked Life Data

1846921

Source:http://linkedlifedata.com/resource/pubmed/id/1846921

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-3-12
pubmed:abstractText
This paper describes the synthesis and structure-activity relationships as kappa opioid analgesics of a novel class of 1-(arylacetyl)-2-(aminomethyl)piperidine derivatives. The active conformation of the pharmacophore, with a torsional angle (N1C2C7N8) of 60 degrees, was defined with computational studies and 1H NMR. A quantitative structure-activity relationship study of the arylacetic moiety substitution indicated that the presence of an electron-withdrawing and lipophilic substituent in para and/or meta positions is required for good analgesic activity and kappa affinity. The lead compounds (2S)-1-[(3,4-dichlorophenyl)acetyl]-2-(pyrrolidin-1-ylmethyl )piperidine hydrochloride and (2S)-1-[4-(trifluoromethyl)phenyl]acetyl]-2-(pyrrolidin-1-ylmet hyl) piperidine hydrochloride are the most kappa/mu selective (respectively 6500:1 and 4100:1) and among the most potent (Ki kappa 0.24 and 0.57 nM, respectively) kappa ligands identified so far. In the mouse tail flick model of antinociception, compound 14 (ED50 = 0.05 mg/kg sc) was 25 times more potent than morphine and 16 times more potent than the standard kappa ligand U-50488.
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:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-403
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
(2S)-1-(arylacetyl)-2-(aminomethyl)piperidine derivatives: novel, highly selective kappa opioid analgesics.
pubmed:affiliation
Zambeletti Research Laboratories, Baranzate, Milan, Italy.
pubmed:publicationType
Journal Article, Comparative Study