CAS 913358-93-7|Almorexant HCI

Introduction:Basic information about CAS 913358-93-7|Almorexant HCI, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Common NameAlmorexant HCI
CAS Number913358-93-7Molecular Weight549.024
Density/Boiling Point/
Molecular FormulaC29H32ClF3N2O3Melting Point/
MSDS/Flash Point/

Names

Name2(1H)​-​Isoquinolineacetamid​e, 3,​4-​dihydro-​6,​7-​dimethoxy-​N-​methyl-​α-​phenyl-​1-​[2-​[4-​(trifluoromethyl)​phenyl]​ethyl]​-​, hydrochloride (1:1)​, (αR,​1S)​
SynonymMore Synonyms

Almorexant HCI BiologicalActivity

DescriptionAlmorexant Hcl (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.
Related CatalogSignaling Pathways >>GPCR/G Protein >>Orexin Receptor (OX Receptor)Research Areas >>Neurological Disease
Target

IC50 value: 1.3/0.7 nM(OX1/OX2 receptor) [1] [2]

In 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].
References

[1]. 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.

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

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

[4]. 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.

[5]. Borniger JC, et al. A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metab. 2018 Jul 3;28(1):118-129.e5.

Chemical & Physical Properties

Molecular FormulaC29H32ClF3N2O3
Molecular Weight549.024
Exact Mass548.205383
PSA50.80000
LogP6.87270
InChIKeyBYGBTDRDPBJUBB-LHIMUUITSA-N
SMILESCNC(=O)C(c1ccccc1)N1CCc2cc(OC)c(OC)cc2C1CCc1ccc(C(F)(F)F)cc1.Cl
Storage condition-20℃

Synonyms

(2R)-2-[(1S)-6,7-Dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydro-2(1H)-isoquinolinyl]-N-methyl-2-phenylacetamide hydrochloride (1:1)
(2R)-2-[(1R)-6,7-Dimethoxy-1-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydro-2(1H)-isoquinolinyl]-N-methyl-2-phenylacetamide hydrochloride (1:1)
Almorexant HCI
2(1H)-Isoquinolineacetamide, 3,4-dihydro-6,7-dimethoxy-N-methyl-α-phenyl-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-, (αR,1R)-, hydrochloride (1:1)
2(1H)-Isoquinolineacetamide, 3,4-dihydro-6,7-dimethoxy-N-methyl-α-phenyl-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-, (αR,1S)-, hydrochloride (1:1)
Act-078573
Almorexant HCl
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