Pimozide

Base Information

• Chemical Name: Pimozide
• CAS No.: 2062-78-4
• Molecular Formula: C28H29 F2 N3 O
• Molecular Weight: 461.555
• Hs Code.: 2933399090
• European Community (EC) Number: 218-171-7
• NSC Number: 757854,170984
• UNII: 1HIZ4DL86F
• DSSTox Substance ID: DTXSID8023474
• Nikkaji Number: J3.698F
• Wikipedia: Pimozide
• Wikidata: Q144085
• NCI Thesaurus Code: C47672
• RXCUI: 8331
• Pharos Ligand ID: QC4NBYGR69YF
• Metabolomics Workbench ID: 43330
• ChEMBL ID: CHEMBL1423
• Mol file: 2062-78-4.mol

Synonyms:Antalon;Orap;Orap forte;Pimozide;R-6238;R6238

Chemical Property of Pimozide

Chemical Property:

• Melting Point: 214-218°
• Boiling Point: °Cat760mmHg
• PKA: 7.32(at 25℃)
• Flash Point: °C
• PSA: 41.03000
• Density: 1.224g/cm³
• LogP: 5.79490
• Storage Temp.: 2-8°C
• Solubility.: DMSO: 18 mg/mL
• Water Solubility.: 2.9mg/L(30 oC)
• XLogP3: 6.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 461.22786888
• Heavy Atom Count: 34
• Complexity: 632

Purity/Quality:

98%,99%, ^*data from raw suppliers

Pimozide ^*data from reagent suppliers

Safty Information:

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antipsychotic Agents
• Canonical SMILES: C1CN(CCC1N2C3=CC=CC=C3NC2=O)CCCC(C4=CC=C(C=C4)F)C5=CC=C(C=C5)F
• Recent ClinicalTrials: Electrophysiological Effects of Potential QT Prolonging Drugs
• Recent EU Clinical Trials: Cognitive effects of adjuntive Vortioxetine in early Schizophrenia
• Description: Pimozide is a dopamine receptor antagonist (Kis = 2.4, 0.3, and 1.8 nM for D2, D3, and D4 receptors, respectively). It also binds to eight additional receptors (Kds = 25-3,100 nM for the human receptors) and inhibits the voltage-gated sodium channel Nav1.2 and the voltage-gated potassium channel Kv11.1 (IC50s = 42 and 340 nM, respectively). Pimozide (0.5, 1, and 2 mg/kg) decreases the number of licks and reduces fluid intake of a sweetened solution in rats. It decreases the number of threats and attacks and increases immobility time in the neutral arena aggression test, indicating increased passiveness, in male mice when administered at a dose of 0.75 mg/kg for 10 days. Formulations containing pimozide have been used in the treatment of Tourette syndrome.
• Uses: Pimozide is a D2 dopamine receptor antagonist that binds to the cloned 5-HT7 receptor with high affinity (1,2,3,4). Pimozide is also a Ca2+ channel antagonist. Pimozide is used as an antipsychotic. Used for the suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond satisfactorily to standard treatment.
• 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 with anti-arrhythmics that prolong the QT interval - avoid with amiodarone and disopyramide (risk of ventricular arrhythmias). Antibacterials: avoid with macrolides and moxifloxacin (increased risk of ventricular arrhythmias). Antidepressants: concentration increased by SSRIs - avoid; increased risk of ventricular arrhythmias with SSRIs and tricyclics - avoid; increased risk of ventricular arrhythmias with delamanid. Antiepileptics: antagonises anticonvulsant effect. Antifungals: avoid with imidazoles and triazoles - risk of ventricular arrhythmias. Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol; increased risk of ventricular arrhythmias with mefloquine and quinine - avoid. Antipsychotics: increased risk of ventricular arrhythmias with droperidol, phenothiazines, risperidone or sulpiride - avoid; concentration possibly increased by lurasidone. Antivirals: concentration increased by atazanavir, boceprevir, efavirenz, fosamprenavir, indinavir, ritonavir, saquinavir and telaprevir, increased risk of ventricular arrhythmias - avoid. Anxiolytics and hypnotics: increased sedative effects. Aprepitant: avoid concomitant use. Atomoxetine: increased risk of ventricular arrhythmias. Beta-blockers: increased risk of ventricular arrhythmias with sotalol. Cobicistat: concentration possibly increased by cobicistat - avoid. Cytotoxics: use crizotinib with caution; avoid with lapatinib and idelalisib; increased risk of ventricular arrhythmias with panobinostat and vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide. Diuretics: increased risk of ventricular arrhythmias due to hypokalaemia. Fosaprepitant: avoid concomitant use. Grapefruit juice: avoid concomitant use. Ivabradine: increased risk of ventricular arrhythmias.

Technology Process of Pimozide

There total 7 articles about Pimozide 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: 97.5%

4-(2-keto-1-benzimidazolinyl)piperidine (20662-53-7) + 4-chloro-1,1-bis(4-fluorophenyl)butane (3312-04-7) → pimozide (2062-78-4)

Guidance literature:

With sodium carbonate; potassium iodide; In 1,3-dioxolane-4-methanol; at 80 ℃; for 7h;

Reference yield: 71.0%

1,1-bis(-4-fluorophenyl)-4-iodobutane (51787-79-2) + 4-(2-keto-1-benzimidazolinyl)piperidine (20662-53-7) → pimozide (2062-78-4)

Guidance literature:

With sodium carbonate; In dichloromethane; acetonitrile; at 80 ℃; for 12h;

DOI:10.1002/chem.201902918

Reference yield:

1,1'-(but-1-ene-4,4-diyl)bis(4-fluorobenzene) (61668-03-9) → pimozide (2062-78-4)

Guidance literature:

Multi-step reaction with 2 steps

1.1: Schwartz's reagent / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere

1.2: 0 - 20 °C / Inert atmosphere

2.1: sodium carbonate / acetonitrile; 1,2-dichloro-ethane / 12 h / Reflux; Inert atmosphere

With Schwartz's reagent; sodium carbonate; In tetrahydrofuran; 1,2-dichloro-ethane; acetonitrile;

DOI:10.1021/acs.orglett.5b01290

upstream raw materials:

4-(2-keto-1-benzimidazolinyl)piperidine

4-chloro-1,1-bis(4-fluorophenyl)butane

1,1'-(but-1-ene-4,4-diyl)bis(4-fluorobenzene)

1,1-bis(-4-fluorophenyl)-4-iodobutane

Downstream raw materials:

Pimozide N-Oxide

Refernces

• 1、 Saito, Masato,Tsuji, Nobuya,Kobayashi, Yusuke,Takemoto, Yoshiji. "Direct Dehydroxylative Coupling Reaction of Alcohols with Organosilanes through Si-X Bond Activation by Halogen Bonding". . p. 3000 - 3003. Retrieved 2015/06/30.