Paroxetine

Base Information

• Chemical Name: Paroxetine
• CAS No.: 61869-08-7
• Deprecated CAS: 63952-24-9
• Molecular Formula: C19H20FNO3
• Molecular Weight: 329.371
• Hs Code.: 2934999090
• UNII: 41VRH5220H,32Q7TW8BX7
• DSSTox Substance ID: DTXSID3023425
• Nikkaji Number: J259.859K
• Wikipedia: Paroxetine
• Wikidata: Q408471
• NCI Thesaurus Code: C61879
• RXCUI: 32937
• Pharos Ligand ID: TPG4Q6ZJ88Z3
• Metabolomics Workbench ID: 43023
• ChEMBL ID: CHEMBL490
• Mol file: 61869-08-7.mol

Synonyms:Aropax;BRL 29060;BRL-29060;BRL29060;FG 7051;FG-7051;FG7051;Paroxetine;Paroxetine Acetate;Paroxetine Hydrochloride;Paroxetine Hydrochloride Anhydrous;Paroxetine Hydrochloride Hemihydrate;Paroxetine Hydrochloride, Hemihydrate;Paroxetine Maleate;Paroxetine, cis-(+)-Isomer;Paroxetine, cis-(-)-Isomer;Paroxetine, trans-(+)-Isomer;Paxil;Seroxat

Chemical Property of Paroxetine

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 2.39E-08mmHg at 25°C
• Melting Point: 114-116 °C
• Refractive Index: 1.561
• Boiling Point: 451.674 °C at 760 mmHg
• PKA: pKa 9.51 (Uncertain)
• Flash Point: 226.964 °C
• PSA: 39.72000
• Density: 1.213 g/cm³
• LogP: 3.65530
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 4
• Exact Mass: 329.14272166
• Heavy Atom Count: 24
• Complexity: 402

Purity/Quality:

98% ^*data from raw suppliers

(3S,4R)-3-((Benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine 97% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antidepressant Agents
• Canonical SMILES: C1CNCC(C1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4
• Isomeric SMILES: C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4
• Recent ClinicalTrials: Vortioxetine in the Elderly vs. Selective Serotonin Reuptake Inhibitors (SSRIs): a Pragmatic Assessment
• Recent EU Clinical Trials: Trial Examining Methods for Antidepressant Discontinuation
• Recent NIPH Clinical Trials: Study of the link between Dopamine Transporter Gene Polymorphisms and Response To Paroxetin and Escitalopram in Patients With Lifelong Premature Ejaculation
• Description: Paroxetine is a new highly selective serotonin reuptake inhibitor, mechanistically similar to fluoxetine, fluvoxamine and sertraline, introduced for the treatment of all types of depressive illnesses including depression associated with anxiety. It is reportedly non-sedating and non-stimulatory and compared to fluoxetine has a shorter duration of action (half-life of 24 hours versus 2 to 3 days). Paroxetine is also being investigated as a treatment for obesity, alcoholism and obsessive-compulsive disorders.
• Uses: A istopically labelled selective serotonin reuptake inhibitor. Used as an antidepressant
• Therapeutic Function: Antidepressant
• Biological Functions: Paroxetine (Paxil) has an elimination half-life of 21 hours and is also highly bound to plasma proteins, so it requires special attention when administered with drugs such as warfarin. Paroxetine is a potent inhibitor of the cytochrome P450 2D6 isoenzyme and can raise the plasma levels of drugs metabolized via this route. Of particular concern are drugs with a narrow therapeutic index, such as TCAs and the type 1C antiarrhythmics flecainide, propafenone, and encainide. Additionally, paroxetine itself is metabolized by this enzyme and inhibits its own metabolism, leading to nonlinear kinetics. Weight gain is higher with paroxetine than with the other SSRIs, and it tends to be more sedating, presumably because of its potential anticholinergic effects. Additionally, patients have had difficulty with abrupt discontinuation with this agent, reporting a flulike syndrome; this symptom can be avoided by tapering the medication.
• Clinical Use: In vitro binding studies suggest that paroxetine is a more selective and potent inhibitor of 5-HT reuptake than fluoxetine. The drug essentially has no effect on NE or dopamine reuptake, nor does it show affinity for other neuroreceptors. Its onset of action is 1 to 4 weeks.
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: increased risk of bleeding with aspirin and NSAIDs; risk of CNS toxicity increased with tramadol; concentration of methadone possibly increased. Anti-arrhythmics: possibly inhibits propafenone metabolism (increased risk of toxicity). Anticoagulants: effect of coumarins possibly enhanced; possibly increased risk of bleeding with dabigatran. Antidepressants: avoid concomitant use with MAOIs and moclobemide (increased risk of toxicity); avoid with St John’s wort; possibly enhanced serotonergic effects with duloxetine; can increase concentration of tricyclics; possible increased risk of convulsions with vortioxetine. Antiepileptics: antagonism (lowered convulsive threshold); concentration reduced by phenytoin and phenobarbital. Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol. Antipsychotics: concentration of clozapine and possibly risperidone increased; metabolism of perphenazine inhibited, reduce dose of perphenazine; possibly inhibits aripiprazole metabolism, reduce aripiprazole dose; concentration possibly increased by asenapine; increased risk of ventricular arrhythmias with pimozide - avoid. Antivirals: concentration possibly reduced by darunavir and ritonavir. Beta blockers: concentration of metoprolol possibly increased - increased risk of AV block - avoid in cardiac insufficiency. Dapoxetine: possible increased risk of serotonergic effects - avoid. Dopaminergics: increased risk of hypertension and CNS excitation with selegiline - avoid; increased risk of CNS toxicity with rasagiline - avoid. Hormone antagonists: metabolism of tamoxifen to active metabolite possibly reduced - avoid. 5HT1 agonists: risk of CNS toxicity increased by sumatriptan - avoid; possibly increased risk of serotonergic effects with naratriptan. Lithium: increased risk of CNS effects - monitor levels. Methylthioninium: risk of CNS toxicity - avoid if possible.

Technology Process of Paroxetine

There total 127 articles about Paroxetine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

C25H25FN2O3 → paroxetine (61869-08-7)

Guidance literature:

With acetic acid; zinc; at 20 ℃; for 6h;

Reference yield: 97.0%

(3S,4R)-1-benzyl-4-(4-fluorophenyl)-3-[3,4-(methylenedioxy)-phenoxymethyl]piperidine (105813-14-7) → paroxetine (61869-08-7)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; acetic acid; isopropyl alcohol; at 50 ℃; for 15h; under 4500.45 Torr; stereoselective reaction;

DOI:10.1002/chem.201603056

Reference yield: 96.0%

(3S,4R)-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)-1-vinyloxycarbonylpiperidine (600135-90-8) → paroxetine (61869-08-7)

Guidance literature:

(3S,4R)-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)-1-vinyloxycarbonylpiperidine; With hydrogenchloride; In 1,2-dichloro-ethane; for 0.75h;

In ethanol; for 1.5h; Heating;

DOI:10.1016/S0045-2068(03)00040-3

upstream raw materials:

(3R,4S)-1-(tert-butoxycarbonyl)-4-(p-fluorophenyl)-3-[3,4-(methylenedioxy)phenoxymethyl]piperidine

(3S,4R)-1-(tert-butoxycarbonyl)-4-(p-fluorophenyl)-3-[3,4-(methylenedioxy)phenoxymethyl]piperidine

(3S,4R)-4-(4-fluorophenyl)-3-hydroxymethylpiperidine-1-carboxylic acid tert-butyl ester

(3S,4R)-tert-butyl 4-(4-fluorophenyl)-3-(((methylsulfonyl)oxy)methyl)piperidine-1-carboxylate

Downstream raw materials:

Desmethylene-Paroxetine

(3S,4R)-3-((benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)-1-methylpiperidine

N-formyl paroxetine ((3S,4R)-3-((benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carbaldehyde)

(-)-paroxetine hydrochloride

Refernces

• 1、 -. "Preparation method of paroxetine and analogues thereof". . . Retrieved 2020/08/25.
• 2、 Szcze?niak, Piotr,Buda, Szymon,Lefevre, Laura,Staszewska-Krajewska, Olga,Mlynarski, Jacek. "Total Asymmetric Synthesis of (+)-Paroxetine and (+)-Femoxetine". . p. 6973 - 6982. Retrieved 2019/11/20.