CAS 871224-64-5|Almorexant

Introduction：Basic information about CAS 871224-64-5|Almorexant, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Almorexant BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	Almorexant
CAS Number	871224-64-5	Molecular Weight	512.563
Density	1.2±0.1 g/cm3	Boiling Point	620.4±55.0 °C at 760 mmHg
Molecular Formula	C₂₉H₃₁F₃N₂O₃	Melting Point	/
MSDS	/	Flash Point	329.0±31.5 °C

Names

Name	(R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
Synonym	More Synonyms

Almorexant BiologicalActivity

Description	Almorexant(ACT078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.IC50 value: 1.3/0.7 nM(OX1/OX2 receptor) [1] [2]Target: Dual OX!/OX2 receptorin vitro: [(3)H]Almorexant bound to a single saturable site on hOX(1) and hOX(2) with high affinity (K(d) of 1.3 and 0.17 nM, respectively. In Schild analyses using the [(3)H]inositol phosphates assay, almorexant acted as a competitive antagonist at hOX(1) and as a noncompetitive-like antagonist at hOX(2). In binding kinetic analyses, [(3)H]almorexant had fast association and dissociation rates at hOX(1), whereas it had a fast association rate and a remarkably slow dissociation rate at hOX(2) [1]. in vivo: During the 12-h dark period after dosing, ALM(Almorexant) exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness [3]. Almorexant 200 mg showed significantly less 'Drug Liking' than both zolpidem doses (p < 0.01), and almorexant 400 mg had smaller effects than zolpidem 20 mg (p < 0.05), while almorexant 1,000 mg was not different from either zolpidem dose [4].
Related Catalog	Signaling Pathways >>GPCR/G Protein >>Orexin Receptor (OX Receptor)Research Areas >>Neurological Disease
References	[1]. Cruz HG, et al. Assessment of the abuse liability of a dual orexin receptor antagonist: a crossover study of almorexant and zolpidem in recreational drug users. CNS Drugs. 2014 Apr;28(4):361-72. [2]. Malherbe P, et al. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31. [3]. Sifferlen T, et al. Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1539-42. [4]. Black SW, et al. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013 Mar 1;36(3):325-36. [5]. Dayot S, et al. In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin-1/orexin-A and almorexant in pancreatic ductal adenocarcinoma. Oncotarget. 2018 Jan 9;9(6):6952-6967.

Description

Almorexant(ACT078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.IC50 value: 1.3/0.7 nM(OX1/OX2 receptor) [1] [2]Target: Dual OX!/OX2 receptorin vitro: [(3)H]Almorexant bound to a single saturable site on hOX(1) and hOX(2) with high affinity (K(d) of 1.3 and 0.17 nM, respectively. In Schild analyses using the [(3)H]inositol phosphates assay, almorexant acted as a competitive antagonist at hOX(1) and as a noncompetitive-like antagonist at hOX(2). In binding kinetic analyses, [(3)H]almorexant had fast association and dissociation rates at hOX(1), whereas it had a fast association rate and a remarkably slow dissociation rate at hOX(2) [1]. in vivo: During the 12-h dark period after dosing, ALM(Almorexant) exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness [3]. Almorexant 200 mg showed significantly less 'Drug Liking' than both zolpidem doses (p < 0.01), and almorexant 400 mg had smaller effects than zolpidem 20 mg (p < 0.05), while almorexant 1,000 mg was not different from either zolpidem dose [4].

Related Catalog

Signaling Pathways >>GPCR/G Protein >>Orexin Receptor (OX Receptor)Research Areas >>Neurological Disease

References

[1]. Cruz HG, et al. Assessment of the abuse liability of a dual orexin receptor antagonist: a crossover study of almorexant and zolpidem in recreational drug users. CNS Drugs. 2014 Apr;28(4):361-72.

[2]. Malherbe P, et al. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol. 2009 Sep;76(3):618-31.

[3]. Sifferlen T, et al. Novel pyrazolo-tetrahydropyridines as potent orexin receptor antagonists. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1539-42.

[4]. Black SW, et al. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Sleep. 2013 Mar 1;36(3):325-36.

[5]. Dayot S, et al. In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin-1/orexin-A and almorexant in pancreatic ductal adenocarcinoma. Oncotarget. 2018 Jan 9;9(6):6952-6967.

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	620.4±55.0 °C at 760 mmHg
Molecular Formula	C₂₉H₃₁F₃N₂O₃
Molecular Weight	512.563
Flash Point	329.0±31.5 °C
Exact Mass	512.228699
PSA	50.80000
LogP	5.89
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.554
InChIKey	DKMACHNQISHMDN-UHFFFAOYSA-N
SMILES	CNC(=O)C(c1ccccc1)N1CCc2cc(OC)c(OC)cc2C1CCc1ccc(C(F)(F)F)cc1

Synonyms

(2R)-2-[(1S)-6,7-Dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydro-2(1H)-isoquinolinyl]-N-methyl-2-phenylacetamide

(R)-2-{(S)-6,7-dimethoxy-1-[2-(4-trifluoromethylphenyl)ethyl]-3,4-dihydro-1H-isoquinolin-2-yl}-N-methyl-2-phenylacetamide

Almorexant [inn]

[3H]-Almorexant

2(1H)-Isoquinolineacetamide, 3,4-dihydro-6,7-dimethoxy-N-methyl-α-phenyl-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-, (αR,1S)-

AlMorexant HCl

2(1H)-Isoquinolineacetamide, 3,4-dihydro-6,7-dimethoxy-N-methyl-α-phenyl-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-, (αR,1R)-

(2R)-2-((1S)-6,7-Dimethoxy-1-{2-(4-(trifluoromethyl)phenyl)ethyl}-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide

Almorexant

(2R)-2-{(1S)-6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydro-1H-isoquinolin-2-yl}-N-methyl-2-phenyl-acetamide

((2R)-2-((1S)-6,7-dimethoxy-1-(2-(4-trifluoromethylphenyl)-ethyl)-3,4-dihydro-1H-isoquinolin-2-yl)-N-methyl-2-phenylacetamide)

(2R)-2-[(1R)-6,7-Dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydro-2(1H)-isoquinolinyl]-N-methyl-2-phenylacetamide

Recommended......