Paliperidone

Base Information

• Chemical Name: Paliperidone
• CAS No.: 144598-75-4
• Deprecated CAS: 130049-84-2,130049-86-4,147687-18-1
• Molecular Formula: C23H27FN4O3
• Molecular Weight: 426.491
• Hs Code.: 29349990
• European Community (EC) Number: 620-493-1
• UNII: 838F01T721
• DSSTox Substance ID: DTXSID7049059
• Nikkaji Number: J508.304D
• Wikipedia: Paliperidone
• Wikidata: Q423292
• NCI Thesaurus Code: C66293
• RXCUI: 679314
• Pharos Ligand ID: L99B6UJ2QS43
• Metabolomics Workbench ID: 43472
• ChEMBL ID: CHEMBL1621
• Mol file: 144598-75-4.mol

Synonyms:3-(2-(4-(6-fluoro-3-(1,2-benzisoxazolyl))-1-piperidinyl)ethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido(1,2-a)pyrimidin-4-one;9 Hydroxy risperidone;9 Hydroxyrisperidone;9 OH risperidone;9-hydroxy-risperidone;9-hydroxyrisperidone;9-OH-risperidone;Invega;Invega Sustenna;paliperidone;paliperidone palmitate;Palmitate, Paliperidone;R 76477;R-76477;R76477;Sustenna, Invega

Chemical Property of Paliperidone

Chemical Property:

• Appearance/Colour: off white to light orange coloured solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 158-160 °C
• Refractive Index: 1.692
• Boiling Point: 612.3 °C at 760 mmHg
• PKA: 13.00±0.60(Predicted)
• Flash Point: 324.1 °C
• PSA: 84.39000
• Density: 1.45 g/cm³
• LogP: 3.01920
• Storage Temp.: Room temp
• Solubility.: DMSO: soluble2mg/mL, clear (warmed)
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 4
• Exact Mass: 426.20671890
• Heavy Atom Count: 31
• Complexity: 764

Purity/Quality:

99% ^*data from raw suppliers

rac 9-Hydroxyrisperidone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T,F
• Statements: 25-39/23/24/25-23/24/25-11
• Safety Statements: 45-36/37-16

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antipsychotic Agents
• Canonical SMILES: CC1=C(C(=O)N2CCCC(C2=N1)O)CCN3CCC(CC3)C4=NOC5=C4C=CC(=C5)F
• Recent ClinicalTrials: Substance Misuse To Psychosis for Stimulants
• Recent EU Clinical Trials: HAMLETT. Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment. A pragmatic single blind RCT of continuation versus discontinuation/ dose reduction of antipsychotic medication in patients remitted after a first episode of psychosis
• Recent NIPH Clinical Trials: Valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia
• Description: Paliperidone, (±)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one(Invega), is essentially insoluble in water and is available asextended-release tablets. Paliperidone is delivered at a constantrate using an osmotic drug release device (OsmoticRelease Oral Systems [OROS]). Paliperidone is FDA-approved for schizophrenia aged 12–17. However, the pharmacologic portfolio, extrapolation from adult studies, and the long track record of the parent drug, risperidone in child/adolescent psychiatric (CAP) population might expand its therapeutic potential. Paliperidone, the C-9 hydroxylated active metabolite of the antipsychotic agent risperidone, is the newest atypical antipsychotic to join the market following the introductions of olanzapine (ZyprexaTM), risperidone (RisperdalTM), quetiapine(SeroquelTM),and ziprasidone (GeodonTM). Compared to its parent, paliperidone has improved PK properties and a reduced potential for drug interactions. In terms of receptor affinity, the two drugs are equipotent.
• Uses: This medication is used to treat certain mental/mood disorders (such as schizophrenia, schizoaffective disorder). This medication can decrease hallucinations and help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life. Paliperidone belongs to a class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain. A metabolite of Risperidone, a combined serotonin (5-HT2) and dopamine (D2) receptor antagonist A metabolite of Risperidone (R525000), a combined serotonin (5-HT2) and dopamine (D2) receptor antagonist. Paliperidone(Invega) is an atypical antipsychotic. Chemically, paliperidone is the primary active metabolite of the older atypical antipsychotic risperidone. It is indicated for the acute and maintenance treatment of schizophrenia
• Clinical Use: Atypical antipsychotic for schizophrenia
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone. Anti-arrhythmics: increased risk of ventricular arrhythmias when given with anti-arrhythmics that prolong the QT interval. Antidepressants: increases concentration of tricyclics (possibly increased risk of ventricular arrhythmias). Antiepileptics: antagonise anticonvulsant effect (convulsive threshold lowered); concentration reduced by carbamazepine. Antimalarials: avoidance of antipsychotics advised by manufacturer of artemether/lumefantrine. Antipsychotics: possible increased risk of ventricular arrhythmias with risperidone. Antivirals: concentration possibly increased by ritonavir. Atomoxetine: increased risk of ventricular arrhythmias with atomoxetine. Cytotoxics: increased risk of ventricular arrhythmias with arsenic trioxide.

Technology Process of Paliperidone

There total 47 articles about Paliperidone 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: 100.0%

paliperidone oxalate (1272320-23-6) → paliperidone (144598-75-4,147663-01-2)

Guidance literature:

With ammonium hydroxide; In water;

Reference yield: 94.5%

3-(2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl)-9-(methoxymethoxy)-2-methyl-6,7,8,9-tetrahydro-pyrido[1,2-α]pyrimidin-4-one → paliperidone (144598-75-4,147663-01-2)

Guidance literature:

With hydrogenchloride; In methanol; water; for 4h; Reflux;

Reference yield: 94.0%

3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (130049-82-0) + 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (84163-13-3) → paliperidone (144598-75-4,147663-01-2)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; In methanol; for 24h; Reflux;

upstream raw materials:

di-isopropyl ether

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride

diisopropylamine

isopropyl alcohol

Downstream raw materials:

3-{2-[4-(4-fluoro-2-hydroxybenzoyl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one

3-{2-[4-(6-fluoro-1,2-benzoisoxazol-3-yl)-piperidin-1-yl]ethyl}-2-methyl-4-oxo-6,7,8,9-tetrahydro-pyrido[1,2-α]pyrimidin-9-yl benzoate

9-O-phenylacetyl chloride paliperidone

3-{2-[4-(6-fluoro-1,2-benzoisoxazol-3-yl)-1-piperidinyl]ethyl}-2-methyl-4-oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-9-yl p-nitrophenyl carbonate

Refernces

• 1、 -. "Synthesis process of paliperidone palmitate". Paragraph 0036-0045; 0051-0060; 0066-0075. . Retrieved 2019/10/04.
• 2、 -. "Paliperidone intermediate and method for producing paliperidone using the same". Paragraph 0095-0096. . Retrieved 2018/06/12.