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Details

Stereochemistry ABSOLUTE
Molecular Formula C29H31F3N2O3.ClH
Molecular Weight 549.024
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALMOREXANT HYDROCHLORIDE

SMILES

Cl.CNC(=O)[C@H](N1CCC2=CC(OC)=C(OC)C=C2[C@@H]1CCC3=CC=C(C=C3)C(F)(F)F)C4=CC=CC=C4

InChI

InChIKey=BYGBTDRDPBJUBB-LHIMUUITSA-N
InChI=1S/C29H31F3N2O3.ClH/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32;/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35);1H/t24-,27+;/m0./s1

HIDE SMILES / InChI
Molecular Formula C29H31F3N2O3
Molecular Weight 512.5632
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20047164

Almorexant (ACT-078573) is an orally active dual orexin receptor antagonist that is being developed by Actelion Ltd, in collaboration with GlaxoSmithKline plc, for the treatment of primary insomnia. Almorexant is a first-in-class compound that targets the orexin system, which plays a key role in wake promotion and stabilization; In January 2011, GlaxoSmithKline (GSK) and Actelion Ltd announced that clinical development of Phase III of almorexant has been discontinued. This decision follows a review of data from additional clinical studies, which were conducted to further establish the clinical profile of almorexant, including the tolerability profile.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
111 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
291 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
115 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
362 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1910 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
638 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.1 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
19 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
15.1 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20376002
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ALMOREXANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P00GTT0
https://www.1pchem.com/search?query=1P00GTT0
AK Scientific
5265AA
https://aksci.com/item_detail.php?cat=5265AA
AK Scientific
SYN5750
https://aksci.com/item_detail.php?cat=SYN5750
Angene
AGN-PC-0WA2J2
http://www.angenechemical.com/productshow/AGN-PC-0WA2J2.html
AOBIOUS INC
AOB87163
http://aobious.com/aobious/search?search_query=AOB87163
AstaTech
86262
http://astatechinc.com/CPSResult.php?CRNO=86262
Cayman Chemical
13638
http://www.caymanchem.com/app/template/Product.vm/catalog/13638
Chem Scene
CS-2484
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2484
Chem Scene
CS-2485
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2485
Combi-Blocks
QK-9736
http://www.combi-blocks.com/cgi-bin/find.cgi?QK-9736
eMolecules
168729771
https://orderbb.emolecules.com/search/#?query=168729771
eMolecules
271446910
https://orderbb.emolecules.com/search/#?query=271446910
eMolecules
44811135
https://orderbb.emolecules.com/search/#?query=44811135
eMolecules
49260429
https://orderbb.emolecules.com/search/#?query=49260429
eMolecules
53925939
https://orderbb.emolecules.com/search/#?query=53925939
eNovation Chemicals
D409755
https://www.enovationchem.com/Products.asp?SEARCHTEXT=D409755&searchbtn.x=0&searchbtn.y=0
KeyOrganics
AS-17049
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17049
Matrix Scientific
100478
http://www.matrixscientific.com/100478.html
mcule
MCULE-1206667795
https://mcule.com/MCULE-1206667795/
mcule
MCULE-2411142079
https://mcule.com/MCULE-2411142079/
mcule
MCULE-5253025975
https://mcule.com/MCULE-5253025975/
mcule
MCULE-9124423481
https://mcule.com/MCULE-9124423481/
MedChem Express
HY-10805
https://www.medchemexpress.com/search.html?q=HY-10805A&ft=&fa=&fp=
MedChem Express
HY-10805A
https://www.medchemexpress.com/search.html?q=HY-10805A&ft=&fa=&fp=
Molnova
M16329
https://www.molnova.com/en/serch-list.html?keywords=M16329
Molnova
M16560
https://www.molnova.com/en/serch-list.html?keywords=M16560
MolPort
MolPort-021-804-912
https://www.molport.com/shop/molecule-link/MolPort-021-804-912
MolPort
MolPort-035-395-893
https://www.molport.com/shop/molecule-link/MolPort-035-395-893
MuseChem
I005246
https://www.musechem.com/product/I005246.html
MuseChem
I005446
https://www.musechem.com/product/I005446.html
MuseChem
M125205
https://www.musechem.com/product/M125205.html
Selleck Chemicals
S2160
http://www.selleckchem.com/search.html?searchDTO.searchParam=S2160
ShangHai Biochempartner
BCP02616
http://www.biochempartner.com/search_BCP02616
ShangHai Biochempartner
BCP08993
http://www.biochempartner.com/search_BCP08993
TargetMol
T2613
https://www.targetmol.com/search?keyword=T2613
TargetMol
T6155
https://www.targetmol.com/search?keyword=T6155
Toronto Research Chemicals
A575195
https://www.trc-canada.com/product-detail/?CatNum=A575195
PubMed

PubMed

TitleDatePubMed
Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant.
2010-10
[The newer sedative-hypnotics].
2010-09
Orexin receptor antagonists: a new concept in CNS disorders?
2010-08-02
Antagonism of rat orexin receptors by almorexant attenuates central chemoreception in wakefulness in the active period of the diurnal cycle.
2010-08-01
Mapping the binding pocket of dual antagonist almorexant to human orexin 1 and orexin 2 receptors: comparison with the selective OX1 antagonist SB-674042 and the selective OX2 antagonist N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).
2010-07
Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant.
2010-05
Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA.
2010-04
Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists.
2010-03-01
Almorexant, a dual orexin receptor antagonist for the treatment of insomnia.
2010-01
Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.
2009-11-13
Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal.
2009-10
Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists.
2009-09
Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat.
2009-07
Emerging therapies for sleep disorders.
2009-06
Molecule of the month. Almorexant.
2009-05
In the arms of Morpheus: Actelion keeps sleepers from waking.
2009-02-27
The evolving story of orexin biology: the hits keep coming.
2009
Orexin receptor antagonists: medicinal chemistry and therapeutic potential.
2008
To sleep, perchance to rest (in the daytime).
2007-04
Promotion of sleep by targeting the orexin system in rats, dogs and humans.
2007-02
Patents

Patents

20070191424
2
JP2010248237A
2

Sample Use Guides

In Vivo Use Guide
Almorexant 200mg or matching placebo (double-blind) was administered orally once daily in the morning for 10 days
Route of Administration: Oral
In Vitro Use Guide
Almorexant inhibits intracellular calcium release in HEK-293 cells expressing either Ox-R1 or Ox-R2. Using the fluorescence based calcium mobilization assay in Human Embryonic Kidney Cells (HEK Cells), full dose-response curves were generated for orexin-A at Ox-and orexin-B at Ox-R2. Almorexant alone did not induce intracellular calcium release at either Ox-R1 or Ox-R2. However Orexin-B (10 nM) induced changes in intracellular calcium fluorescence at the Ox-R2 receptor, were dose-dependently inhibited by almorexant (concentration range: 10 pM-100 µM).
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:06:12 GMT 2025
Edited
by admin
on Mon Mar 31 23:06:12 GMT 2025
Record UNII
O4Z94D9A99
Record Status Validated (UNII)
Record Version
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Name Type Language
ACT-078573 HYDROCHLORIDE
Preferred Name English
ALMOREXANT HYDROCHLORIDE
Common Name English
2(1H)-ISOQUINOLINEACETAMIDE, 3,4-DIHYDRO-6,7-DIMETHOXY-N-METHYL-.ALPHA.-PHENYL-1-(2-(4-(TRIFLUOROMETHYL)PHENYL)ETHYL)-, HYDROCHLORIDE (1:1), (.ALPHA.R,1S)-
Systematic Name English
Code System Code Type Description
PUBCHEM
25227440
Created by admin on Mon Mar 31 23:06:12 GMT 2025 , Edited by admin on Mon Mar 31 23:06:12 GMT 2025
PRIMARY
FDA UNII
O4Z94D9A99
Created by admin on Mon Mar 31 23:06:12 GMT 2025 , Edited by admin on Mon Mar 31 23:06:12 GMT 2025
PRIMARY
CAS
913358-93-7
Created by admin on Mon Mar 31 23:06:12 GMT 2025 , Edited by admin on Mon Mar 31 23:06:12 GMT 2025
PRIMARY
Related Record Type Details
Structure of ALMOREXANT
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of ALMOREXANT
ACTIVE MOIETY
NIH
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