Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors

被引：41

作者：

Yao, Zhangyu ^{[1
]}

Wei, Xueying ^{[1
]}

Wu, Xiaoming ^{[1
]}

Katz, Jonathan L. ^{[2
]}

Kopajtic, Theresa ^{[2
]}

Greig, Nigel H. ^{[3
]}

Sun, Hongbin ^{[1
]}

机构：

[1] China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing 210009, Peoples R China

[2] Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[3] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 05期

关键词：

Tetrabenazine enantiomers; Dihydrotetrabenazine stereoisomers; Resolution; Huntington's chorea; VMAT2; Hyperkinetic disorders; MONOAMINE TRANSPORTER; MOVEMENT-DISORDERS; METABOLITE; EPOXIDES; EMETINE; BINDING; DRUGS;

D O I：

10.1016/j.ejmech.2011.02.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 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. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：1841 / 1848

页数：8

共 50 条

[41] Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes
Naganawa, Mika
Lim, Keunpoong
Nabulsi, Nabeel B.
Lin, Shu-fei
Labaree, David
Ropchan, Jim
Herold, Kevan C.
Huang, Yiyun
Harris, Paul
Ichise, Masanori
Cline, Gary W.
Carson, Richard E.
MOLECULAR IMAGING AND BIOLOGY, 2018, 20 (05) : 835 - 845
[42] Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes
Mika Naganawa
Keunpoong Lim
Nabeel B. Nabulsi
Shu-fei Lin
David Labaree
Jim Ropchan
Kevan C. Herold
Yiyun Huang
Paul Harris
Masanori Ichise
Gary W. Cline
Richard E. Carson
Molecular Imaging and Biology, 2018, 20 : 835 - 845
[43] Deuterated 18F-9-O-hexadeutero-3-fluoropropoxyl-(+)dihydrotetrabenazine (D6-FP-(+)-DTBZ): A vesicular monoamine transporter 2 (VMAT2) imaging agent
Liu, Futao
Choi, Seok Rye
Zha, Zhihao
Ploessl, Karl
Zhu, Lin
Kung, Hank F.
NUCLEAR MEDICINE AND BIOLOGY, 2018, 57 : 42 - 49
[44] Depression and suicidality with VMAT2 inhibitors in tardive dyskinesia A signal detection from the FDA Adverse Events Reporting System
Yokoi, Yuma
Kashiwagi, Hiroko
Funada, Daisuke
Yamashita, Shingo
Kubota, Chika
PSYCHIATRY AND CLINICAL NEUROSCIENCES REPORTS, 2023, 2 (01):
[45] CHART EXTRACTION/CLINICIAN SURVEY SHOWS SYMPTOM IMPACT AND FAVORABLE TREATMENT OUTCOMES WITH VMAT2 INHIBITORS IN PATIENTS WITH TARDIVE DYSKINESIA
Lundt, L.
Franey, E.
Yonan, C.
PARKINSONISM & RELATED DISORDERS, 2020, 79 : E119 - E119
[46] Chart Extraction/Clinician Survey Shows Symptom Impact and Favorable Treatment Outcomes with VMAT2 Inhibitors in Patients with Tardive Dyskinesia
Lundt, Leslie
Franey, Ericha
Yonan, Chuck
NEUROLOGY, 2020, 94 (15)
[47] Divergent de novo synthesis of all eight stereoisomers of 2,3,6-trideoxyhexopyranosides and their oligomers
Song, Wangze
Zhao, Yu
Lynch, John C.
Kim, Hyunjin
Tang, Weiping
CHEMICAL COMMUNICATIONS, 2015, 51 (98) : 17475 - 17478
[48] Effects of VMAT2 inhibitors lobeline and GZ-793A on methamphetamine-induced changes in dopamine release, metabolism and synthesis in vivo
Meyer, Andrew C.
Neugebauer, Nichole M.
Zheng, Guangrong
Crooks, Peter A.
Dwoskin, Linda P.
Bardo, Michael T.
JOURNAL OF NEUROCHEMISTRY, 2013, 127 (02) : 187 - 198
[49] Risk of VMAT2 inhibitors on suicidality and parkinsonism: report utilizing the United States Food and Drug Administration adverse event reporting system
Wong, Sabrina
Le, Gia Han
Kwan, Angela T. H.
Rhee, Taeho Greg
Teopiz, Kayla M.
Ho, Roger C.
Cao, Bing
Rosenblat, Joshua D.
Mansur, Rodrigo
Mcintyre, Roger S.
INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY, 2025, 40 (03) : 176 - 181
[50] The effects of acute administration of VMAT2 inhibitors on extracellular levels of dopamine, norepinephrine, 5-HT and histamine in the striatum and medial prefrontal cortex
Adler, E.
Magid, L.
Even-Chen, O.
Schmidt, S.
Cope, I.
Alexander, J.
Kehr, J.
Orbach, A.
MOVEMENT DISORDERS, 2021, 36 : S124 - S125

← 1 2 3 4 5 →