SELTOREXANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H22FN7O
Molecular Weight	407.4441
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CN(C[C@]1([H])CN(C2)C3=NC(C)=CC(C)=N3)C(=O)C4=C(C=CC=C4F)N5N=CC=N5

InChI

InChIKey=SQOCEMCKYDVLMM-IYBDPMFKSA-N

InChI=1S/C21H22FN7O/c1-13-8-14(2)26-21(25-13)28-11-15-9-27(10-16(15)12-28)20(30)19-17(22)4-3-5-18(19)29-23-6-7-24-29/h3-8,15-16H,9-12H2,1-2H3/t15-,16+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29848147 | https://www.ncbi.nlm.nih.gov/pubmed/30644312 | https://adisinsight.springer.com/drugs/800040115 | http://www.minervaneurosciences.com/innovation-pipeline/min-202/

2-(4,6-DIMETHYLPYRIMIDIN-2-YL)-5-((2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)CARBONYL)OCTAHYDROPYRROLO(3,4-C)PYRROLE (Seltorexant, MIN 202), a small molecule, selective orexin receptor type-2 antagonist, is being developed by Minerva Neurosciences and Janssen Research & Development for the treatment of insomnia and major depressive disorder. Seltorexant has shown high in vitro affinity (affinity pKi =8.0 and 6.1 for OX2R and OX1R respectively) for the human OX2R and approximates two logs selectivity ratio versus its affinity for the OX1R. Seltorexant demonstrated a dose-dependent normalization of sleep and a trend towards improvement of subjective depressive symptoms in antidepressant-treated MDD patients with residual insomnia. Additionally, seltorexant’s favorable PK profile as a potential sedative-hypnotic drug was confirmed in a MDD population and did not demonstrate unacceptable adverse events or unwanted next-day CNS effects. Seltorexant is in phase II clinical trials for both insomnia and MDD.

CNS Activity

Originator

Approval Year

PubMed

Title	Date	PubMed
A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.	2018 Jun	29848147
The selective orexin-2 receptor antagonist seltorexant improves sleep: An exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia.	2019 Feb	30644312

Sample Use Guides

In Vivo Use Guide

Twenty male and female patients received a single dose of 10, 20, 40 mg seltorexant and placebo with a washout period of seven days in a double-blind four-way crossover study.

Route of Administration: Oral

In Vitro Use Guide

Seltorexant has shown high in vitro affinity (affinity pKi =8.0 and 6.1 for OX2R and OX1R respectively) for the human OX2R and approximates two logs selectivity ratio versus its affinity for the OX1R.

Name

Type

Language

SELTOREXANT

Official Name

English

JNJ-42847922

Code

English

(5-(4,6-DIMETHYL-2-PYRIMIDINYL)HEXAHYDROPYRROLO(3,4-C)PYRROL-2(1H)-YL)(2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)METHANONE

Systematic Name

English

((3AR,6AS)-5-(4,6-DIMETHYLPYRIMIDIN- 2-YL)HEXAHYDROPYRROLO(3,4-C)PYRROL-2(1H)-YL)(2-FLUORO- 6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)METHANONE OREXIN RECEPTOR ANTAGONIST

Common Name

English

Seltorexant [WHO-DD]

Common Name

English

METHANONE, ((3AR,6AS)-5-(4,6-DIMETHYL-2-PYRIMIDINYL)HEXAHYDROPYRROLO(3,4-C)PYRROL-2(1H)-YL)(2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)-, REL-

Common Name

English

SELTOREXANT [USAN]

Common Name

English

2-(4,6-DIMETHYLPYRIMIDIN-2-YL)-5-((2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)CARBONYL)OCTAHYDROPYRROLO(3,4-C)PYRROLE

Systematic Name

English

MIN-202

Code

English

METHANONE, (5-(4,6-DIMETHYL-2-PYRIMIDINYL)HEXAHYDROPYRROLO(3,4-C)PYRROL-2(1H)-YL)(2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)-

Systematic Name

English

seltorexant [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C265