128196-01-0

Basic information

• Product Name: Escitalopram
• Synonyms: (S)-(+)-CITALOPRAM OXALATE;(1R)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-3H-isobenzofuran-5-carbonitrile;1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile;Escitalopram;(S)-CITALOPRAM S-(+)-1-3-(diMethyl-aMino) propyl-1-(p-fluorophenyl)-5-phthalancarbonitrile;EscitalopraM Oxalate INN;Seroplex;S-(+)-1-3-(dimethyl-amino) propyl-1-(p-fluorophenyl)-5-phthalancarbonitrile
• CAS NO: 128196-01-0
• Molecular Formula: C₂₀H₂₁FN₂O
• Molecular Weight: 414.43
• Product Categories: API
• Mol File: 128196-01-0.mol
• Article Data: 41

Chemical Properties

• Boiling Point: 428.3 °C at 760 mmHg
• Flash Point: 212.8 °C
• Appearance: white or white crystalline powder
• Density: 1.18 g/cm³
• Vapor Pressure: 8.04E-15mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO
• PKA: 9.57±0.28(Predicted)
• CAS DataBase Reference: Escitalopram(CAS DataBase Reference)
• NIST Chemistry Reference: Escitalopram(128196-01-0)
• EPA Substance Registry System: Escitalopram(128196-01-0)

Safety Data

• Hazardous Substances Data: 128196-01-0(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 128196-01-0 differently. You can refer to the following data:
1. antidepressive;selective serotonin reuptake inhibitor
2. (S)-Citalopram is an inhibitor of serotonin (5-HT) uptake. Antidepressant.

Definition

ChEBI: A 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile that has S-configuration at the chiral centre. It is the active enantiomer of citalopram.

Biological Activity

escitalopram （lexapro，cipralex）is a selective inihibitor of serotonin(5-ht) reuptake (ssri) with a ki value of 6.6nm for [3h]-5-ht uptake [1].escitalopram is the s-(+)-enantiomer of citalopram and has the inhibition of [3h]-5-ht uptake and [125i]-rti-55 binding in cos-1 cells expressing the human serotonin transporter (5-htt) with ki values of 6.6±1.4nm and 3.9±2.2nm, respectively. in addition, escitalopram has been reported to inhibit the accumulation of 3h-labelled monoamines into rat brain synaptosomes in vitro with ic50 values of 2.1±0.75nm, 2500±202nm and 40000±15500nm for [3h]-5-ht, [3h]-i-na and [3h]-da, respectively. apart from these, escitalopram has shown the in vitro affinity for rat histamine h1 receptors and the rat sigma σ1 site with ki values of 1500±780nm and 100±71nm, respectively [1].

Mechanism of action

Escitalopram is the S-enantiomer of citalopram that binds with high affinity and selectivity to the human SERT equivalent to (±)-citalopram. It has been reported that nearly all the activity resides in the S-enantiomer and that R-citalopram actually counteracts the action of the S-enantiomer. Studies show that escitalopram exhibits twice the activity of citalopram and is at least 27 times more potent than the R-enantiomer. The R-enantiomer inhibits the S-enantiomer at the transporter. Escitalopram's mechanism of action is common to the SSRIs.

Pharmacokinetics

The pharmacokinetics for escitalopram does not exhibit stereoisomer selectivity and, therefore, is similar to that for citalopram. Likewise, it exhibits linear pharmacokinetics so that plasma levels increase proportionately and predictably with increased doses, and its half-life of 27 to 32 hours is consistent with once-daily dosing. It also has been found that R-citalopram is cleared more slowly than the S-enantiomer. Therefore, when the drug is used as a racemic mixture (citalopram), the inactive isomer predominates at steady state. This is an added incentive for use of the enantiomerically pure escitalopram. Escitalopram has negligible effects on CYP isoforms, suggesting a low potential for drug–drug interactions. Escitalopram is indicated for patients with major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder.

Clinical Use

SSRI antidepressant:Depressive illnessPanic and social anxiety disorder

Drug interactions

Potentially hazardous interactions with other drugsAnalgesics: increased risk of bleeding with aspirin and NSAIDs; risk of CNS toxicity increased with tramadol.Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone, disopyramide and dronedarone - avoid.Antibacterials: increased risk of ventricular arrhythmias with IV erythromycin, moxifloxacin, pentamidine and telithromycin.Anticoagulants: effect of coumarins possibly enhanced; possibly increased risk of bleeding with dabigatran.Antidepressants: avoid concomitant use with MAOI, increased risk of toxicity; increased risk of CNS toxicity with moclobemide - avoid concomitant use; avoid concomitant use with St John’s wort; possibly enhanced serotonergic effects with dapoxetine and duloxetine; can increase concentration of tricyclics; increased agitation and nausea with tryptophan; increased risk of CNS toxicity with rasagiline; possible increased risk of convulsions with vortioxetineAntiepileptics: convulsive threshold lowered.Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid.Antimalarials: avoid concomitant use with artemether/lumefantrine and piperaquine with artenimol; possible increased risk of ventricular arrhythmias with chloroquine and quinine.Antipsychotics: possibly increased risk of ventricular arrhythmias with haloperidol, phenothiazines and pimozide - avoid.Antivirals: concentration possibly increased by ritonavir.Beta-blockers: increased risk of ventricular arrhythmias with sotalol - avoid.Dopaminergics: avoid with selegiline; increased risk of CNS toxicity with rasagiline.5HT1 agonist: increased risk of CNS toxicity with sumatriptan; possibly increased risk of serotonergic effects with naratriptan.Linezolid: use with care, possibly increased risk of side effects.Lithium: increased risk of CNS effectsMethylthioninium: risk of CNS toxicity - avoid if possible.

Metabolism

Escitalopram is metabolised in the liver to the demethylated and didemethylated metabolites. Both of these are pharmacologically active. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent substance and metabolites are partly excreted as glucuronides. After multiple dosing the mean concentrations of the demethyl and didemethyl metabolites are usually 28-31% and <5%, respectively, of the escitalopram concentration. Biotransformation of escitalopram to the demethylated metabolite is mediated primarily by CYP2C19. Some contribution by the enzymes CYP3A4 and CYP2D6 is possible. The major metabolites have a significantly longer half-life than the parent drug.Escitalopram and major metabolites are assumed to be eliminated by both hepatic and renal routes, with the major part of the dose excreted as metabolites in the urine.

references

[1] sánchez c1, bergqvist pb, brennum lt, gupta s, hogg s, larsen a, wiborg o. escitalopram, the s-(+)-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities. psychopharmacology (berl). 2003 jun;167(4):353-62. epub 2003 apr 26.

InChI:InChI=1/C20H21FN2O.C2H2O4/c1-23(2)11-3-10-20(17-5-7-18(21)8-6-17)19-9-4-15(13-22)12-16(19)14-24-20;3-1(4)2(5)6/h4-9,12H,3,10-11,14H2,1-2H3;(H,3,4)(H,5,6)

Upstream product

• 852705-13-6 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-5-bromo-1,3-dihydroisobenzofuran methanesulfonate salt 
• 544-92-3 copper(I) cyanide 
• 852705-11-4 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-5-bromo-1,3-dihydroisobenzofuran benzoate salt 
• 852705-14-7 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-5-bromo-1,3-dihydroisobenzofuran trifluoromethanesulfonate salt 
• 852705-15-8 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-5-bromo-1,3-dihydroisobenzofuran perchlorate salt 
• 852705-10-3 C₂H₄O₂*C₁₉H₂₁BrFNO 
• 166037-78-1 (+)-Didemethylcitalopram 
• 50-00-0 formaldehyd 
• 64-18-6 formic acid 
• 863116-45-4 succinic acid mono-{5-cyano-2-[(S)-4-dimethylamino-1-(4-fluorophenyl)-1-hydroxybutyl]-benzyl} ester 
• 144025-14-9 (+)-Desmethylcitalopram 
• 905710-66-9 4-bromo-3-(hydroxymethyl)benzonitrile 
• 254744-14-4 2-bromo-5-cyanobenzyl acetate 
• 1352344-84-3 C₁₃H₁₄BrNO₂ 

Downstream Products

• 1116112-98-1 S-citalopram hydrochloride 
• 219861-08-2 escitalopram oxalate 
• 128173-53-5 (S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (+)-di-p-toluoyltartaric acid salt 
• 440121-09-5 C₂₀H₂₂FNO₃ 
• 1329745-98-3 (S)-4-dimethylamino-1-{1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl}-1-butanone 
• 1585941-35-0 (S)-2-(6-(diethylamino)-3-(diethyliminio)-3H-xanthen-9-yl)-5-(N-(6-(((1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)methyl)amino)-6-oxohexyl)sulfamoyl)benzenesulfonate 
• 1585941-33-8 (S)-3-(5-(aminomethyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N,N-dimethylpropan-1-amine 
• 936846-17-2 C₂₀H₂₂FNO₂ 
• 1425794-07-5 C₂₂H₂₂ClFN₂O₃ 
• 1425794-11-1 (S)-(3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)dimethylsulfonium trifluoromethanesulfonate 
• 1425794-12-2 (S)-1-(4-fluorophenyl)-1-(3-(methyselanyl)propyl)-1,3-dihydroisobenzofuran-5-carbonitrile 
• 1425794-09-7 (S)-1-(4-fluorophenyl)-1-(3-(methylthio)propyl)-1,3-dihydroisobenzofuran-5-carbonitrile 
• 144025-14-9 (+)-Desmethylcitalopram 
• 1425794-14-4 (S)-(3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)propyl)dimethylselenonium trifluoromethanesulfonate 

Relevant articles and documents

A Photoswitchable Inhibitor of the Human Serotonin Transporter

The human serotonin transporter (hSERT) terminates serotonergic signaling through reuptake of neurotransmitter into presynaptic neurons and is a target for many antidepressant drugs. We describe here the development of a photoswitchable hSERT inhibitor, termed azo-escitalopram, that can be reversibly switched between trans and cis configurations using light of different wavelengths. The dark-adapted trans isomer was found to be significantly less active than the cis isomer, formed upon irradiation.

Enzymatic resolution of a quaternary stereogenic centre as the key step in the synthesis of (S)-(+)-citalopram

The enzymatic resolution of 4-[(4-dimethylamino)-1-(4′-fluorophenyl)- 1-hydroxy-1-butyl]-3-(hydroxymethyl)-benzonitrile, a useful intermediate in the synthesis of enantiomerically pure citalopram, has been studied. Candida antarctica lipase B (CAL-B) catalyzes the enzymatic acetylation of the primary benzylic alcohol with high enantioselectivity at the quaternary stereogenic centre. The enzymatic enantioselective hydrolysis of the 3-acetyloxymethyl derivative catalyzed by CAL-B is also possible.

Method for preparing citalopram and S - citalopram

The invention relates to a method of preparing citalopram and S-citalopram by carrying out cyclization reaction on a diol compound (II) or S-diol compound (II') in a nixed solvent of a C4-C7 ketone solvent and water and aryl sulfonyl chloride or alkyl sulfonyl chloride under an alkaline condition. The solvent used by the invention is great in solubility to reactants and products, so that the use level of the solvent is reduced, the yield is improved and meanwhile the method is good in post-treatment extraction effect and simple and convenient to operate. The compounds (II and II') are as shown in the specification.

PROCESS FOR PRODUCING HYDROBROMIDE OF DIOL COMPOUND

PROBLEM TO BE SOLVED: To provide a method for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide with a high purity and a high isolation yield. SOLUTION: Provided is a process for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide characterized in bringing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile and hydrogen bromide into contact in a mixed solvent of an ester-based solvent and water. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT