deutetrabenazine   

GtoPdb Ligand ID: 8707

Synonyms: Austedo® | SD-809 | SD809 | tetrabenazine D6
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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Physico-chemical Properties
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
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]