Linked Life Data

2155320

Source:http://linkedlifedata.com/resource/pubmed/id/2155320

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1990-4-6
pubmed:abstractText
A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine [( 3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (Ki greater than 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (Ki = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR less than 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/Ki) = -5.83F + 0.64 pi + 7.41 (r = 0.90).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1069-76
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Synthesis and structure-activity relationship of C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+-)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site.
pubmed:affiliation
Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't