Linked Life Data

21396745

Source:http://linkedlifedata.com/resource/pubmed/id/21396745

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-28
pubmed:abstractText
Tetrabenazine (TBZ) ((±)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (±)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (Ki=4.47 nM) was 8000-fold more potent than (-)-1 (Ki=36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: Ki=3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1768-3254
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1841-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors.
pubmed:affiliation
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural