Ontology highlight
ABSTRACT:
SUBMITTER: Yao Z
PROVIDER: S-EPMC6191844 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
Yao Zhangyu Z Wei Xueying X Wu Xiaoming X Katz Jonathan L JL Kopajtic Theresa T Greig Nigel H NH Sun Hongbin H
European journal of medicinal chemistry 20110223 5
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 pla ...[more]