Linked Life Data

7636847

Source:http://linkedlifedata.com/resource/pubmed/id/7636847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1995-9-12
pubmed:abstractText
The design and synthesis of peptide mimetics of thyrotropin-releasing hormone (TRH) in which the peptide backbone is entirely replaced by a cyclohexane framework are described. The cis-1,3,5-trisubstituted ring was expected to permit key pharmacophoric groups to adopt conformations consistent with proposed bioactive conformations of the peptide. Compounds were synthesized by a stereoselective synthesis starting from L-glutamic acid. In a behavioral model of cognition in which TRH is active, the mimetics are potent, active compounds, exhibiting oral activity. One analog (26, (1S,3R,5(2S),5S)-5-[[5-oxo-1-(phenylmethyl)-2-pyrrolidinyl]-methyl]-5- [(1H-imidazol-5-yl)methyl]cyclohexaneacetamide) was radiolabeled for binding studies and evaluated in other binding assays and pharmacological tests. Competition binding of 26 vs [3H]MeTRH to rat brain slices suggests a two-site model for ligand binding with IC50's of 1 microM and 3 mM. Direct binding of [3H]-26 shows a biphasic curve with IC50's of 80 and 49 microM, respectively. Further studies would be needed to establish a link between the novel binding site(s) and the behavioral activity of 26 and TRH analogs.
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
21
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2866-79
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Peptide mimetics of thyrotropin-releasing hormone based on a cyclohexane framework: design, synthesis, and cognition-enhancing properties.
pubmed:affiliation
Chemistry Research Department, Hoffmann-La Roche Inc., Roche Research Center, Nutley, New Jersey 07110, USA.
pubmed:publicationType
Journal Article