3466-75-9

Usage

Uses

Used in Pharmaceutical Industry:
(+)-ALPHA-DIHYDROTETRABENAZINE is used as a therapeutic agent for the treatment of movement disorders such as chorea associated with Huntington's disease. Its ability to inhibit synaptic vesicular serotonin uptake helps in reducing the hyperkinetic movement symptoms associated with these disorders.
Used in Neuroscientific Research:
(+)-ALPHA-DIHYDROTETRABENAZINE is used as a research tool for studying the role of VMAT2 in the regulation of monoamine storage and release in the brain. Its high affinity binding to various brain regions allows researchers to investigate the mechanisms underlying neurodegenerative diseases and develop potential therapeutic strategies.
Used in Drug Development:
(+)-ALPHA-DIHYDROTETRABENAZINE serves as a lead compound in the development of new drugs targeting VMAT2 for the treatment of various neurological and psychiatric disorders. Its unique binding properties and inhibitory effects on serotonin uptake make it a promising candidate for further research and drug design.

InChI:InChI=1/C19H29NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16-17,21H,5-7,10-11H2,1-4H3

Upstream product

• 1346909-18-9 4-methyl-2-(3-(trimethylsilyl)prop-1-ene-2-yl)pentyl-4-methylbenzenesulfonate 
• 1346909-10-1 6,7-dimethoxy-2-(4-methyl-2-(3-(trimethylsilyl)prop-1-ene-2-yl)pentyl)-1,2,3,4-tetrahydroisoquinoline 
• 1346909-36-1 methyl 4-methyl-2-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)pentanoate 
• 1346909-38-3 N-methoxy-N,4-dimethyl-2-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)pentane amide 
• 1346909-30-5 5-methyl-3-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)hexan-2-one 
• 1346909-40-7 5-methyl-3-(((tetrahydro-2H-pyran-2-yl)oxy)methyl)hex-1-ene-2-yl trifluoromethanesulfonate 
• 1346909-31-6 3-(hydroxymethyl)-5-methylhex-1-ene-2-yl trifluoromethanesulfonate 
• 1346909-44-1 4-methyl-2-(3-(trimethylsilyl)prop-1-ene-2-yl)pentan-1-ol 
• 58-46-8 (3R^*,11bR^*)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzoquinolizin-2-one 
• 403804-65-9 rac-2-(hydroxymethyl)-4-methylpentanoic acid methyl ester 
• 718635-93-9 tetrabenazine 
• 1745-07-9 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 91342-74-4 3-[(dimethylamino)methyl]-5-methylhexan-2-one 
• 20232-39-7 3,4-dihydro-6,7-dimethoxyisoquinoline hydrochloride 

Downstream Products

• 862287-32-9 C₂₉H₃₆F₃NO₅ 
• 862287-31-8 C₂₉H₃₆F₃NO₅ 
• 862287-34-1 C₂₉H₃₆F₃NO₅ 
• 862287-35-2 C₂₉H₃₆F₃NO₅ 
• 5220-98-4 (+/-)-9-O-desmethyldihydrotetrabenazine 
• 1639208-54-0 (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl (S)-2-amino-3-methylbutanoate di(4-methylbenzenesulfonate) 
• 1207716-61-7 C₂₆H₃₂N₂O₇ 

Relevant academic research and scientific papers

Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific

The two enantiomers of α-dihydratetrabenazine were separated using chiral high performance liquid chromatography. The (+)-isomer showed high affinity in vitro (K(i) - 0.97 ± 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (K(i) = 2.2 ± 0.3 μM). Each isomer was then synthesized in carbon-11 labeled form, and regional brain biodistributions in mice determined after intravenous injection. Only (+)-α-dihydrotetrabenazine showed selective and specific accumulations in regions of dense monoaminergic innervation (e.g., striatum, hypothalamus), which could be blocked by coinjection of unlabeled tetrabenazine. Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is thus stereospecific.

PROCESSES FOR THE SYNTHESIS OF VALBENAZINE

The present application relates to processes for making (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl (S)-2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), which is an inhibitor of vesicular monoamine transporter 2 (VMAT2) useful in the treatment of hyperkinetic movement disorders such as tardive dyskinesia (TD).

SOLID STATE FORMS OF VALBENAZINE

Solid state forms of Valbenazine, Valbenazine salts, processes for preparation thereof and pharmaceutical compositions thereof are disclosed. Processes for the preparation of Valbenazine and intermediates in the preparation thereof are further described.

SYNTHETIC METHODS FOR PREPARATION OF (S)-(2R,3R,11bR)-3-ISOBUTYL-9,10-DIMETHOXY-2,3,4,6,7,11b-HEXAHYDRO-1H-PYRIDO[2,1-a]ISOQUINOLIN-2-YL 2-AMINO-3-METHYLBUTANOATE DI(4-METHYLBENZENESULFONATE)

Provided herein are processes for the preparation of (S)-(2R,3R,11bR-3-isobuty-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate), or a solvate, hydrate, or polymorph thereof.

Synthesis of (±)-Tetrabenazine by Visible Light Photoredox Catalysis

(±)-Tetrabenazine was synthesized in six steps from commercially available compounds. The key cyclization substrate was assembled rapidly via Baylis-Hillman and aza-Michael reactions. Annulation of the final ring was achieved through visible light photocatalysis, wherein carbon-carbon bond formation was driven by the oxidation of a tertiary amine. Solvent played a critical role in the photoredox cyclization outcome, whereas methanol led to a mixed ketal, acetonitrile/water (10:1) gave direct cyclization to (±)-tetrabenazine and occurred more rapidly.

METHOD OF PREPARING TETRABENAZINE AND DIHYDROTETRABENAZINE

The present invention relates to a method for preparing tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ), and more specifically to a method for preparing tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ) by using simple and short reaction processes o

Synthesis and X-ray analysis of dihydrotetrabenazine, a metabolite of tetrabenazine

The dihydrotetrabenazine (DTBZ) was synthesized by reduction of tetrabenazine with sodium borohydride in ethanol. Crystals suitable for X-ray analysis were obtained from a mixed solution of dichloromethane and ethanol in a five-to-one volume ratio. The crystal is monoclinic, space group P 21c with crystallographic parameters: a = 15.0129(14), b = 12.5677(12), c = 9.7715(9), = 98.556(2), = 0.078 mm1, V = 1823.1(3) 3, Z = 4, Dc = 1.164 g/cm3, F(000) = 696, T = 296(2) K. The X-ray analysis and the chiral HPLC show that the DTBZ prepared by our method consists of (2R,3R,11bR) and (2S,3S,11bS) enantiomers. Taylor and Francis Group, LLC.

A concise synthesis of tetrabenazine: An intramolecular aza-prins-type cyclization via oxidative c-h activation

A concise synthesis of tetrabenazine and dihydrotetrabenazine is described. The key feature of this synthesis is the intramolecular aza-Prins-type cyclization of an amino allylsilane via oxidative C-H activation. 2011 American Chemical Society.

Synthesis of (+)-and (-)-tetrabenazine from the resolution of-dihydrotetrabenazine

Tetrabenazine (1) was reduced with NaBH4 to-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)-and (-)-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (-)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.

RADIOLABELED DIHYDROTETRABENAZINE DERIVATIVES AND THEIR USE AS IMAGING AGENTS

This invention relates to a method of imaging vesicular monoamine transporters and to labeled compounds and pharmaceutical compositions thereof, and methods of making labeled compounds useful in imaging vesicular monoamine transporters. This invention als