Linked Life Data

21714510

Source:http://linkedlifedata.com/resource/pubmed/id/21714510

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2011-8-4
pubmed:abstractText
To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8?-axial, 8?-equatorial, and 7?-equatorial were synthesized by photochemical cyclization of appropriately substituted N-benzoyl enamines, and the 7?-axial analogue was prepared by an intramolecular Henry reaction. All of the methylated analogues displayed losses in affinity when compared to DHX (20 nM): 8?-Me(ax)-DHX (270 nM), 8?-Me(eq)-DHX (920 nM), 7?-Me(eq)-DHX (6540 nM), and 7?-Me(ax)-DHX (>10000 nM). Molecular modeling studies suggest that although the disruption of an aromatic interaction between Phe203(5.47) and Phe288(6.51) is the cause for the 14-fold loss in affinity associated with 8?-axial substitution, unfavorable steric interactions with Ser107(3.36) result in the more dramatic decreases in binding affinity suffered by the rest of the analogues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5508-21
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Probing the steric space at the floor of the D1 dopamine receptor orthosteric binding domain: 7?-, 7?-, 8?-, and 8?-methyl substituted dihydrexidine analogues.
pubmed:affiliation
Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural