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

• ChemBase编号: 971
• 分子式: C28H29F2N3O
• 平均质量: 461.5461664
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 1-{1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one
• IUPAC传统名: pimozide
• 商标名: Halomonth; Neoperidole; Opiran; Orap
• 别名: 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

登记号

• CAS号: 2062-78-4
• EC号: 218-171-7
• MDL号: MFCD00055081
• PubChem SID: 24277923; 160964434; 46507096
• PubChem CID: 16362
• CHEBI ID: 8212
• ATC码: N05AG02
• CHEMBL: 1423
• Chemspider ID: 15520
• DrugBank ID: DB01100
• IUPHAR配体索引: 90
• KEGG ID: D00560
• 美国药典/FDA物质标识码: 1HIZ4DL86F
• 维基百科标题: Pimozide
• Medline Plus: a686018

理论计算性质

JChem

• Acid pKa: 12.898585
• 质子受体: 2
• 质子供体: 1
• LogD (pH = 5.5): 3.0353284
• LogD (pH = 7.4): 4.8004894
• Log P: 5.8257136
• 摩尔折射率: 132.2078 cm^3
• 极化性: 49.5421 Å^3
• 极化表面积: 35.58 Å^2
• 可自由旋转的化学键: 7
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 6.36
• LOG S: -5.43
• 溶解度: 1.73e-03 g/l

分子性质

理化性质

• 溶解度: 10 mg/L; DMSO: soluble18 mg/mL; H2O: insoluble
• 熔点: 215-218°C
• 疏水性(logP): 5.6

安全信息

• 保存条件: Room Temperature (15-30°C)
• RTECS编号: DE1750000
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 联合国危险货物编号: 2811
• 德国WGK号: 3
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): III
• 澳大利亚Hazchem: 2X
• 危险公开号: 22; R:22
• 安全公开号: 36; S:36/37/39
• 欧盟危险货物分类: T2
• 欧盟危险识别号(EUHIN): 6.1B
• 美国ERG指导号: 154
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H302
• 保存温度: 2-8°C

药理学性质

• 作用靶点: Others
• 给药途径: oral only
• 生物利用度: at least 40 to 50%
• 排泄: urine, and to a lesser extent in feces
• 半衰期: 2 to 3 days (average in one study 55 hours)
• 代谢: hepatic, by cytochrome P450, isoenzymes 3A, and 1A2; metabolites are inactive
• 法定药品分级: Rx-only, not a controlled narcotic
• 妊娠期药物分类: Teratogenic data in rats exist : drug should only be used when the benefit clearly exceeds the potential harm to the unborn
• 相关基因信息: 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)

产品相关信息

• 纯度: 98%
• 成盐信息: Free Base

详细说明

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.

参考文献

• 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