(R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
(R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide Basic information
- Product Name:
- (R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
- Synonyms:
-
- (R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
- Almorexant
- 2-(6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
- (2R)-2-[(1S)-6,7-DIMETHOXY-1-[2-[4-(TRIFLUOROMETHYL)PHENYL]ETHYL]-3,4-DIHYDRO-1H-ISOQUINOLIN-2-YL]-N-METHYL-2-PHENYLACETAMIDE
- almorexant (ACT-078573)
- almorexant (ACT-078573), CID 23727689
- 3,4-Dihydro-6,7-dimethoxy-N-methyl-alpha-phenyl-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-2(1H)-isoquinolineacetamide
- (2R)-2-((1S)-6,7-Dimethoxy-1-{2-(4-(trifluoromethyl)phenyl)ethyl}-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
- CAS:
- 871224-64-5
- MF:
- C29H31F3N2O3
- MW:
- 512.56
- Product Categories:
-
- Inhibitors
- API intermediates
- Mol File:
- 871224-64-5.mol
(R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide Chemical Properties
- Boiling point:
- 620.4±55.0 °C(Predicted)
- Density
- 1.205
- storage temp.
- Desiccate at -20°C
- solubility
- Soluble in DMSO
- form
- Powder
- pka
- 15.04±0.46(Predicted)
- color
- White to off-white
(R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide Usage And Synthesis
Uses
Almorexant is a dual orexin receptor antagonist ACT-541468 used in the treatment of insomnia. It regulates sleep and wakefulness through two G protein-coupled receptors, namely Orexin 1 receptor and Orexin 2 receptor.
Definition
ChEBI: Almorexant is a member of isoquinolines.
Biological Activity
almorexant is an antagonist of orexin 1 receptor (ox1r) and orexin 2 receptor (ox2r) with kd values of 1.3nm and 0.17nm, respectively [1].almorexant is a dual ox antagonist. it inhibits the binding of orexin-a to both ox1r and ox2r with ic50 values of 6.6nm and 3.4nm, respectively. in the inositol phosphates assay, almorexant acts as a competitive antagonist of hox1r but a noncompetitive-like antagonist of hox2r. besides that, almorexant is found to block the increase in locomotor activity induced by icv orexin in c57bl/6 mice. furthermore, almorexant shows effects on sleep in multiple species, including man. it reduces the time spent awake and increased the time spent in nrem and rem sleep dose-dependently in normal c57bl/6 mice. these effects on sleep caused by almorexant are mediated by ox2rs as almorexant has no effect in mice lacking both ox1r and ox2r but has effects in mice lacking only ox1r [1, 2].
in vivo
Almorexant (1.8 μmol/kg, 100 μL; IP, daily) reduces the volume of tumors[2].
Almorexant (300 mg/kg, PO, once) can help rats to be fully capable of spatial and avoidance learning[4].
Almorexant (30-300 mg/kg) dose-dependently increases rapid eye movement (REM) and non-REM (NREM) sleep and decreases wakefulness apparently without inducing either cataplexy18 or deficits in next-day performance[3].
| Animal Model: | Mice xenografted with AsPC-1 cells[2] |
| Dosage: | 1.8 μmol/kg, 100 μL |
| Administration: | IP, daily, starting at day 0 or day 38 |
| Result: | Resulted in a significant decrease in tumor volume when treatment starting at day 0. Started after AsPC-1 tumors were developed (day 38), rapidly and strongly reduced the volume of established tumors. |
| Animal Model: | Long-Evans rats (24, male, 16-18 weeks of age)[4] |
| Dosage: | 300 mg/kg |
| Administration: | PO, once |
| Result: | Successfully learned the spatial task, established spatial memory. |
| Animal Model: | Male C57BL/6 mice (Orexin/ataxin-3 transgenic (TG) mice and WT mice, 32 ± 0.9 g, age 15 ± 0.5 week)[3] |
| Dosage: | 30, 100, 300 mg/kg (3, 10, and 30 mg/mL; 10 mL/kg) |
| Administration: | IP, once every 3 days |
| Result: | Exacerbated cataplexy in TG mice and increased nonrapid eye movement (NREM) sleep with heightened sleep/wake fragmentation in both genotypes during the 12-h dark period after dosing. Showed greater hypnotic potency in WT mice than in TG mice. |
IC 50
human OX2R: 0.17 nM (Kd); human OX1R: 1.3 nM (Kd); Caspase-3
References
[1] malherbe p, borroni e, pinard e, wettstein jg, knoflach f. 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] mang gm1, dürst t, bürki h, imobersteg s, abramowski d, schuepbach e, hoyer d, fendt m, gee ce. the dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors. sleep. 2012 dec 1;35(12):1625-35.
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