3466-75-9

Basic information

• Product Name: (+)-ALPHA-DIHYDROTETRABENAZINE
• Synonyms: (+)-ALPHA-DIHYDROTETRABENAZINE;2H-BENZO[A]QUINOLIZINE-2-OL, 1,3,4,6,7,11B-HEXAHYDRO-3-ISOBUTYL-9,10-DIMETHOXY-;DIHYDROTETRABENAZINE;DTBZ;2H-Benzo[a]quinolizin-2-ol, 1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-;1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol;(+)-ALPHA-DIHYDROTETRABEZINE
• CAS NO: 3466-75-9
• Molecular Formula: C₁₉H₂₉NO₃
• Molecular Weight: 319.44
• Mol File: 3466-75-9.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 457.8 °C at 760 mmHg
• Flash Point: 230.7 °C
• Appearance: /
• Density: 1.13 g/cm³
• Vapor Pressure: 3.56E-09mmHg at 25°C
• Refractive Index: 1.561
• CAS DataBase Reference: (+)-ALPHA-DIHYDROTETRABENAZINE(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-ALPHA-DIHYDROTETRABENAZINE(3466-75-9)
• EPA Substance Registry System: (+)-ALPHA-DIHYDROTETRABENAZINE(3466-75-9)

Safety Data

• Hazardous Substances Data: 3466-75-9(Hazardous Substances Data)

Usage

Description

Dihydrotetrabenazine is an active metabolite of the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine that is generated by hepatic carbonyl reductases. Dihydrotetrabenazine binds to mouse pons medulla, hypothalamus, and striatum (Kds = 2.72, 2.28, and 2.4 nM, respectively) and inhibits synaptic vesicular serotonin (5-HT) uptake (IC50s = 2.2, 2.8, and 2.3 nM, respectively). It also binds to human caudate nucleus, hippocampus, and substantia nigra pars compacta (Kds = 2.9, 2.5, and 2.8 nM, respectively). Dihydrotetrabenazine stereoisomers bind to VMAT2 in rat striatum.

Chemical Properties

Colourless solid

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

• 58-46-8 (3R^*,11bR^*)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzoquinolizin-2-one 
• 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 
• 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 
• 20232-39-7 3,4-dihydro-6,7-dimethoxyisoquinoline hydrochloride 
• 91342-74-4 3-[(dimethylamino)methyl]-5-methylhexan-2-one 

Downstream Products

• 5220-98-4 (+/-)-9-O-desmethyldihydrotetrabenazine 
• 862287-32-9 C₂₉H₃₆F₃NO₅ 
• 862287-31-8 C₂₉H₃₆F₃NO₅ 
• 862287-34-1 C₂₉H₃₆F₃NO₅ 
• 862287-35-2 C₂₉H₃₆F₃NO₅ 
• 1207716-61-7 C₂₆H₃₂N₂O₇ 
• 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) 

Relevant articles and documents

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.

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.

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.