871224-64-5

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;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;Act-078573;Almorexant [inn];AlMorexant HCl;2(1H)-IsoquinolineacetaMide,3,4-dihydro-6,7-diMethoxy-N-Methyl-a-phenyl-1-[2-[4-(trifluoroMethyl)phenyl]ethyl]-, (aR,1S)-
• CAS NO: 871224-64-5
• Molecular Formula: C₂₉H₃₁F₃N₂O₃
• Molecular Weight: 512.56
• Product Categories: API intermediates;Inhibitors
• Mol File: 871224-64-5.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 620.4 °C at 760 mmHg
• Flash Point: 329 °C
• Appearance: /
• Density: 1.205
• Solubility: Soluble in DMSO
• PKA: 15.04±0.46(Predicted)
• CAS DataBase Reference: (R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide(871224-64-5)
• EPA Substance Registry System: (R)-2-((R)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide(871224-64-5)

Safety Data

• Hazardous Substances Data: 871224-64-5(Hazardous Substances Data)

Usage

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.

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].

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.

Upstream product

• 132283-68-2 2-(2-chloroethyl)-4,5-dimethoxybenzaldehyde 
• 1609564-22-8 (S)-tert-butyl-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1609564-20-6 (S)-tert-butyl 1-(2-hydroxy-2-(4-(trifluoromethyl)phenyl)ethyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 884337-44-4 (S)-1-allyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 
• 181220-97-3 (S)-1-allyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 1415385-75-9 (S)-1-allyl-2-((R)-tert-butylsulfinyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 1415385-74-8 (R)-N-((S)-1-(2-(2-chloroethyl)-4,5-dimethoxyphenyl)but-3-enyl)-2-methylpropane-2-sulfinamide 
• 324076-69-9 6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydroiso-quinoline 
• 871224-68-9 (S)-2-(methylamino)-2-oxo-1-phenylethyl 4-methylbenzenesulfonate 
• 769172-81-8 (S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-1,2,3,4-tetrahydroisoquinoline 
• 51685-62-2 N-methyl-2-bromo-2-phenylethanamide 
• 871224-77-0 {(1S)-6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydro-1H-isoquinolin-2-yl}-phenyl-acetic acid 
• 593-51-1 methylamine hydrochloride 

Downstream Products

• 913358-93-7 almorexant hydrochloride 

Relevant articles and documents

Stereoselective total synthesis of almorexant

A highly stereoselective synthesis of almorexant has been achieved using (R)-tert-butanesulfinamide as a chiral source. The chiral tetrahydroisoquinoline core was constructed through allylation of chiral N-sulfinyl imine followed by ring closure of the se

PROCESS FOR THE PREPARATION OF AN ENANTIOMERIC TRISUBSTITUTED 3,4-DIHYDRO-ISOQUINOLINE DERIVATIVE

The present invention relates to a process for the preparation of the compound of formula (7) which process comprises the hydrogenation of the compound of formula (4) using bis[chloro-1,5-cyclooctadiene-iridium], (S)-i-dicyclohexylphosphino-2-[(S)-α-(dime

TRISUBSTITUTED 3,4-DIHYDRO-1H-ISOQUINOLIN COMPOUND, PROCESS FOR ITS PREPARATION, AND ITS USE

The present invention relates to the compound of formula 7*acetate (see below), a process for its preparation, and its use