Linked Life Data

17618123

Source:http://linkedlifedata.com/resource/pubmed/id/17618123

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2007-7-16
pubmed:abstractText
Two hundred and ten tertiary amides were prepared on solid phase. Diamines were coupled to activated carboxylated Wang polymer, and the polymeric substituted benzyloxycarbonyl protected diamines obtained were reacted with aldehydes or ketones in trimethyl orthoformate giving resin attached Schiff bases. Coupled resins were then reduced to secondary amines by sodium cyanoborohydride in 4% acetic acid/trimethyl orthoformate, followed by acylation with the carboxylic acid in the presence of PyBroP and diisopropylethylamine. Cleavage of tertiary amides from the resin was made by trifluoroacetic acid in the presence of scavengers (mainly 1,2-ethanedithiol). When indole derivatives were prepared, parallel alkylation with the linker fragment occurred, giving derivatives of 2-(4-hydroxybenzyl)-indole as side products. Solution synthesis or mixed liquid/solid phase preparation of title substances proved to be advantageous in cases when the above method did not give acceptable results. According to this approach an efficient formation of Schiff bases was achieved in the presence of TiCl(4). Substances were isolated by reversed phase chromatography; in some cases isomers were additionally separated by chiral chromatography on Chirobiotic T. When tested on human recombinant melanocortin receptors all the tertiary amides showed some binding affinities; for the highest affinity compounds the K(i)s reached 400 nM on MC(1), 2 microM on MC(3) and 1 microM on MC(4) and MC(5) receptors. cAMP assays of some of the title compounds showed that the tertiary amides are melanocortin receptor antagonists on the four MC receptor subtypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5787-810
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Design and synthesis of a library of tertiary amides: evaluation as mimetics of the melanocortins' active core.
pubmed:affiliation
Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala Biomedical center, Uppsala University, Uppsala, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't