ulotaront   Click here for help

GtoPdb Ligand ID: 10454

Synonyms: example 129 [WO2011069063A2] [6] | SEP-363856 (parent molecule) | SEP-856 | SEP363856
PDB Ligand
Compound class: Synthetic organic
Comment: Ulotaront (SEP-363856) is an orally active and brain-penetrant psychotropic agent with a novel mechanism of action. It acts as a trace amine-associated receptor 1 (TAAR1) agonist with additional 5-HT1A receptor agonist activity, and agonism at both of these receptors appears to be required for its clinical effects [2-3]. SEP-363856 is being developed by Sunovion Pharmaceuticals and PsychoGenics, and was granted FDA Breakthrough Therapy Designation as an anti-schizophrenia therapeutic in May 2019. The lack of D2 receptor activity distinguishes SEP-363856 from current antipsychotic medications.
In the Dedic et al. article from 2019 SEP-363856 refers to the hydrochloride salt. We show the parent molecule here. This S enantiomer is more active at TAAR1 compared to the R stereoenantiomer [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 49.5
Molecular weight 183.07
XLogP 0.51
No. Lipinski's rules broken 0
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Canonical SMILES CNCC1OCCc2c1scc2
Isomeric SMILES CNC[C@@H]1OCCc2c1scc2
InChI InChI=1S/C9H13NOS/c1-10-6-8-9-7(2-4-11-8)3-5-12-9/h3,5,8,10H,2,4,6H2,1H3/t8-/m0/s1
1. Correll CU, Koblan KS, Hopkins SC, Li Y, Heather Dworak, Goldman R, Loebel A. (2021)
Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study.
NPJ Schizophr, 7 (1): 63. [PMID:34887427]
2. Dedic N, Jones PG, Hopkins SC, Lew R, Shao L, Campbell JE, Spear KL, Large TH, Campbell UC, Hanania T et al.. (2019)
SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action.
J Pharmacol Exp Ther, 371 (1): 1-14. [PMID:31371483]
3. Heffernan MLR, Herman LW, Brown S, Jones PG, Shao L, Hewitt MC, Campbell JE, Dedic N, Hopkins SC, Koblan KS et al.. (2022)
Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia.
ACS Med Chem Lett, 13 (1): 92-98. [PMID:35047111]
4. Krogmann A, Peters L, von Hardenberg L, Bödeker K, Nöhles VB, Correll CU. (2019)
Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities.
CNS Spectr, 24 (S1): 38-69. [PMID:31482779]
5. Kwan C, Huot P. (2022)
An overview of the active clinical trials for Parkinson's disease psychosis.
Neurodegener Dis Manag, 12 (4): 165-170. [PMID:35592949]
6. Shao L, Campbell JE, Hewitt MC, Campbell U, Hanania TG. (2011)
Multicyclic compounds and methods of use thereof.
Patent number: WO2011069063A2. Assignee: Pgi Drug Discovery LLC, Sunovion Pharmaceuticals Inc. Priority date: 04/12/2009. Publication date: 09/06/2011.