1-{1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one

• ChemBase ID: 971
• Molecular Formular: C28H29F2N3O
• Molecular Mass: 461.5461664
• Monoisotopic Mass: 461.227869
• SMILES: Fc1ccc(C(CCCN2CCC(n3c4c([nH]c3=O)cccc4)CC2)c2ccc(F)cc2)cc1
• Canonical SMILES: Fc1ccc(cc1)C(c1ccc(cc1)F)CCCN1CCC(CC1)n1c(=O)[nH]c2c1cccc2
• InChI: InChI=1S/C28H29F2N3O/c29-22-11-7-20(8-12-22)25(21-9-13-23(30)14-10-21)4-3-17-32-18-15-24(16-19-32)33-27-6-2-1-5-26(27)31-28(33)34/h1-2,5-14,24-25H,3-4,15-19H2,(H,31,34)
• InChIKey: YVUQSNJEYSNKRX-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-{1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one
• IUPAC Traditional name: pimozide
• Brand Name: Halomonth; Neoperidole; Opiran; Orap
• Synonyms: Pimozidum [INN-Latin]; Pimozida [INN-Spanish]; Pimozide; Pimozide; 1-[1-[4,4-Bis(p-fluorophenyl)butyl]-4-piperidyl]-2-benzimidazolinone; 1-[4,4-Bis(p-fluorophenyl)butyl]-4-(2-oxo-1-benzimidazolinyl)piperidine; NSC 170984; Orap; Primozide; R 6238; 1-(1-(4,4-bis(4-fluorophenyl)butyl)-4-piperidinyl)-1,3-dihydro-2h-benzimidazol-2-one; 1-[1-[4,4-Bis(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Database IDs

• CAS Number: 2062-78-4
• EC Number: 218-171-7
• MDL Number: MFCD00055081
• PubChem SID: 24277923; 160964434; 46507096
• PubChem CID: 16362
• CHEBI ID: 8212
• ATC CODE: N05AG02
• CHEMBL: 1423
• Chemspider ID: 15520
• DrugBank ID: DB01100
• IUPHAR ligand ID: 90
• KEGG ID: D00560
• Unique Ingredient Identifier: 1HIZ4DL86F
• Wikipedia Title: Pimozide
• Medline Plus: a686018

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.898585
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 3.0353284
• LogD (pH = 7.4): 4.8004894
• Log P: 5.8257136
• Molar Refractivity: 132.2078 cm^3
• Polarizability: 49.5421 Å^3
• Polar Surface Area: 35.58 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 6.36
• LOG S: -5.43
• Solubility (Water): 1.73e-03 g/l

PROPERTIES

Physical Property

• Solubility: 10 mg/L; DMSO: soluble18 mg/mL; H2O: insoluble
• Melting Point: 215-218°C
• Hydrophobicity(logP): 5.6

Safety Information

• Storage Condition: Room Temperature (15-30°C)
• RTECS: DE1750000
• European Hazard Symbols: Harmful (Xn)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: III
• Australian Hazchem: 2X
• Risk Statements: 22; R:22
• Safety Statements: 36; S:36/37/39
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: Others
• Admin Routes: oral only
• Bioavailability: at least 40 to 50%
• Excretion: urine, and to a lesser extent in feces
• Half Life: 2 to 3 days (average in one study 55 hours)
• Metabolism: hepatic, by cytochrome P450, isoenzymes 3A, and 1A2; metabolites are inactive
• Legal Status: Rx-only, not a controlled narcotic
• Pregnancy Category: Teratogenic data in rats exist : drug should only be used when the benefit clearly exceeds the potential harm to the unborn
• Gene Information: human ... ABCB1(5243), CACNA1G(8913), CYP3A4(1576), DRD2(1813), HTR7(3363), KCNH1(3756), KCNH2(3757), OPRD1(4985)mouse ... Abcb1a(18671), Abcb1b(18669)rat ... Scnn1g(24768)

Product Information

• Purity: 98%
• Salt Data: Free Base

DETAILS

MP Biomedicals - 02153787

Calcium channel antagonist.

DrugBank - DB01100

• Drug Groups: approved
• Description: A diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to haloperidol for the suppression of vocal and motor tics in patients with Tourette syndrome. Although the precise mechanism of action is unknown, blockade of postsynaptic dopamine receptors has been postulated. (From AMA Drug Evaluations Annual, 1994, p403)
• Indication: Used for the suppression of motor and phonic tics in patients with Tourette's Disorder who have failed to respond satisfactorily to standard treatment.
• Pharmacology: Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide's therapeutic and untoward effects. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized. Pimozide also has less potential for inducing sedation and hypotension as it has more specific dopamine receptor blocking activity than other neuroleptic agents (and is therefore a suitable alternative to haloperidol).
• Toxicity: LD₅₀ = 1100 mg/kg (rat, oral), 228 mg/kg (mouse, oral)
• Affected Organisms: Humans and other mammals
• Biotransformation: Notable first-pass metabolism in the liver, primarily by N-dealkylation via the cytochrome P450 isoenzymes CYP3A and CYP1A2 (and possibly CYP2D6). The activity of the two major metabolites has not been determined.
• Absorption: Greater than 50% absorption after oral administration. Serum peak appears 6-8 hours post ingestion.
• Half Life: 29 ± 10 hours (single-dose study of healthy volunteers).
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - P1793

Biochem/physiol Actions
D2 dopamine receptor antagonist; binds with high affinity to the cloned 5-HT7 receptor; Ca2+ channel antagonist; antipsychotic

Toronto Research Chemicals - P447800

Pimozide is a D2 dopamine receptor antagonist. Pimozide binds with high affinity to the cloned 5-HT7 receptor. Pimozide is also a Ca2+ channel antagonist. Pimozide is used as an antipsychotic.

REFERENCES

• Liu, J., et al.: Br. J. Pharmacol., 126, 245 (1999)
• Richelson, E., et al.: Life Sci., 68, 29 (1999)
• Santi, C., et al.: J. Neurosci., 22, 396 (1999)
• Mariot, P., et al.: J. Biol. Chem., 277, 10824 (1999)
• Nikonenko, I., et al.: Mol. Pharmacol., 68, 84 (2