deutetrabenazine   Click here for help

GtoPdb Ligand ID: 8707

Synonyms: Austedo® | SD-809 | SD809 | tetrabenazine D6
Approved drug
deutetrabenazine is an approved drug (FDA (2017))
Compound class: Synthetic organic
Comment: This is an orally available, deuterated analogue of tetrabenazine which can be administered in lower doses and in a simplified dosing regimen. Deutetrabenazine is the first ever deuterated drug to be approved.

In drug discovery, replacing hydrogen atoms in drug compounds with deuterium (deuteration) is a technique employed to inhibit degradation of the drug and its active metabolites. The presence of the deuterium atoms attenuates CYP2D6-driven metabolic breakdown of the compound. This effects an increase in circulating half-lives and improves the duration of therapeutic effect and decreases the dose required to achieve therapeutic concentration [4].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 38.77
Molecular weight 317.2
XLogP 2.65
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COc1cc2c(cc1OC)CCN1C2CC(=O)C(C1)CC(C)C
Isomeric SMILES CC(C[C@@H]1CN2CCc3c([C@H]2CC1=O)cc(c(c3)OC([2H])([2H])[2H])OC([2H])([2H])[2H])C
InChI InChI=1S/C19H27NO3/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/h8-9,12,14,16H,5-7,10-11H2,1-4H3/t14-,16-/m1/s1/i3D3,4D3
InChI Key MKJIEFSOBYUXJB-VFJJUKLQSA-N
References
1. Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojärvi J, Jarskog LF, Jimenez-Shahed J, Kumar R, McEvoy JP et al.. (2017)
Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial.
Lancet Psychiatry, 4 (8): 595-604. [PMID:28668671]
2. Claassen DO, Carroll B, De Boer LM, Wu E, Ayyagari R, Gandhi S, Stamler D. (2017)
Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease.
J Clin Mov Disord, 4: 3. [PMID:28265459]
3. Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Meltzer HY, Woods SW, Bega D, LeDoux MS et al.. (2017)
Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study.
Neurology, 88 (21): 2003-2010. [PMID:28446646]
4. Gant TG. (2014)
Using deuterium in drug discovery: leaving the label in the drug.
J Med Chem, 57 (9): 3595-611. [PMID:24294889]
5. Geschwind MD, Paras N. (2016)
Deutetrabenazine for Treatment of Chorea in Huntington Disease.
JAMA, 316 (1): 33-5. [PMID:27380339]
6. Huntington Study Group. (2006)
Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial.
Neurology, 66 (3): 366-72. [PMID:16476934]
7. Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D et al.. (2016)
Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial.
JAMA, 316 (1): 40-50. [PMID:27380342]