1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

• ChemBase编号: 1038
• 分子式: C35H38Cl2N8O4
• 平均质量: 705.63342
• 单一同位素质量: 704.2393071
• SMILES: Clc1c([C@@]2(O[C@H](CO2)COc2ccc(N3CCN(CC3)c3ccc(n4c(=O)n(nc4)C(CC)C)cc3)cc2)Cn2ncnc2)ccc(Cl)c1
• Canonical SMILES: CCC(n1ncn(c1=O)c1ccc(cc1)N1CCN(CC1)c1ccc(cc1)OC[C@H]1CO[C@](O1)(Cn1cncn1)c1ccc(cc1Cl)Cl)C
• InChI: InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
• InChIKey: VHVPQPYKVGDNFY-ZPGVKDDISA-N

名称和登记号

名称

• IUPAC标准名: 1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
• IUPAC传统名: itraconazole
• 商标名: Itrizole; Oriconazole; Sporal; Sporanos; Sporanox; Sporonox; Triasporn; Hyphanox
• 别名: ITC; ITCZ; ITR; Itraconazol [Spanish]; Itraconazolum [Latin]; ITZ; itraconazole; Itraconazole; Sporanox; 1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one; (+/-)-4-[4-[4-[4-[[(2R,4S)-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one; Itrizole; Oriconazole; R-51211; Sporamelt; Triasporin

登记号

• CAS号: 84625-61-6
• MDL号: MFCD00865619
• PubChem SID: 160964501; 46505954
• PubChem CID: 55283
• CHEBI ID: 6076
• ATC码: J02AC02
• CHEMBL: 22587
• Chemspider ID: 49927
• DrugBank ID: DB01167
• KEGG ID: D00350
• 美国药典/FDA物质标识码: 304NUG5GF4
• 维基百科标题: Itraconazole
• Medline Plus: a692049

理论计算性质

JChem

• 质子受体: 9
• 质子供体: 0
• LogD (pH = 5.5): 7.3001556
• LogD (pH = 7.4): 7.3112283
• Log P: 7.3113713
• 摩尔折射率: 200.4 cm^3
• 极化性: 71.596016 Å^3
• 极化表面积: 100.79 Å^2
• 可自由旋转的化学键: 11
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 5.48
• LOG S: -4.86
• 溶解度: 9.64e-03 g/l

分子性质

理化性质

• 溶解度: Chloroform; Insoluble
• 外观: White and Off-White Solid
• 熔点: 164-166°C
• 疏水性(logP): 5.99; 6.5

安全信息

• 保存条件: -20°C; -20°C Freezer

药理学性质

• 给药途径: Oral and i.v. (US), Oral only (UK)
• 生物利用度: 55%, maximal if taken with full meal
• 半衰期: 21 hours
• 代谢: hepatic (CYP3A4)
• 蛋白结合率: 99.8%
• 法定药品分级: POM (UK); Rx-only (US)
• 妊娠期药物分类: C (safety unknown)

产品相关信息

• 纯度: 95%
• 成盐信息: Free Base

详细说明

DrugBank - DB01167

• Drug Groups: approved; investigational
• Description: One of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]
• Indication: For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
• Pharmacology: Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.
• Toxicity: No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
• Affected Organisms: Fungi, yeast and protozoans
• Biotransformation: Itraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission.
• Absorption: The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
• Half Life: 21 hours
• Protein Binding: 99.8%
• Elimination: Itraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.
• Distribution: * 796 ± 185 L
• Clearance: * 381 +/- 95 mL/minute [IV administration]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S2476

Research Area: Infection
Biological Activity:
Itraconazole(Sporanox) is a triazole antifungal agent. It has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against Aspergillus, which fluconazole is not. It inhibits the fungal cytochrome P450 oxidase-mediated synthesis of ergosterol. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications. [1]

Toronto Research Chemicals - I937500

An orally active antimycotic structurally related to Ketoconazole. Antifungal.

参考文献

• http://en.wikipedia.org/wiki/Itraconazole
• Espinel-Ingroff, A., et al.: Antimicrob. Agents Chemother., 26, 5 (1984)
• Heykants, J., et al.: Mycoses, 32, Suppl 1, 67 (1984)
• Sugar, A.M.,et al.: Curr. Clin. Top. Infect. Dis., 13, 74 (1984)