ALMOREXANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H31F3N2O3
Molecular Weight	512.5632
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=DKMACHNQISHMDN-RPLLCQBOSA-N

InChI=1S/C29H31F3N2O3/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)/t24-,27+/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.abnnewswire.net/press/en/54225/
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

Targets

Primary Target	Pharmacology	Condition	Potency
Orexin receptor 2 Target ID: CHEMBL3307226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20047164	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary insomnia 5 Sources: https://clinicaltrials.gov/ct2/show/NCT00608985	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
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
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
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

Value	Dose	Analyte	Population
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
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
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

T_1/2

Value	Dose	Analyte	Population
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
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
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

Vendor/Aggregator	ID	URL
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
AOBIOUS INC	AOB87163	http://aobious.com/aobious/search?search_query=AOB87163
Angene	AGN-PC-0WA2J2	http://www.angenechemical.com/productshow/AGN-PC-0WA2J2.html
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
KeyOrganics	AS-17049	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17049
Matrix Scientific	100478	http://www.matrixscientific.com/100478.html
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=
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
Molnova	M16329	https://www.molnova.com/en/serch-list.html?keywords=M16329
Molnova	M16560	https://www.molnova.com/en/serch-list.html?keywords=M16560
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
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
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/

PubMed

Title	Date	PubMed
To sleep, perchance to rest (in the daytime).	2007 Apr	17380133
Promotion of sleep by targeting the orexin system in rats, dogs and humans.	2007 Feb	17259994
Orexin receptor antagonists: medicinal chemistry and therapeutic potential.	2008	18673167
The evolving story of orexin biology: the hits keep coming.	2009	20563314
In the arms of Morpheus: Actelion keeps sleepers from waking.	2009 Feb 27	19245999
Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat.	2009 Jul	19363060
Emerging therapies for sleep disorders.	2009 Jun	19516208
Molecule of the month. Almorexant.	2009 May	19536367
Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.	2009 Nov 13	19779148
Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal.	2009 Oct	19811530
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 Sep	19542319
Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA.	2010 Apr	20177882
Antagonism of rat orexin receptors by almorexant attenuates central chemoreception in wakefulness in the active period of the diurnal cycle.	2010 Aug 1	20547681
Orexin receptor antagonists: a new concept in CNS disorders?	2010 Aug 2	20544785
Almorexant, a dual orexin receptor antagonist for the treatment of insomnia.	2010 Jan	20047164
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 Jul	20404073
Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists.	2010 Mar 1	20144866
Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant.	2010 May	20376002
Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant.	2010 Oct	20631993
[The newer sedative-hypnotics].	2010 Sep	20945020

Patents

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).

Name

Type

Language

ALMOREXANT

Official Name

English

Almorexant [WHO-DD]

Common Name

English

(2R)-2-((1S)-6,7-DIMETHOXY-1-(2-(4-(TRIFLUOROMETHYL)PHENYL)ETHYL)-3,4-DIHYDROISOQUINOLIN-2(1H)-YL)-N-METHYL-2-PHENYLACETAMIDE

Systematic Name

English

almorexant [INN]

Common Name

English

ALMOREXANT [MI]

Common Name

English

ACT-078573

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29728