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 ID: 1038
• Molecular Formular: C35H38Cl2N8O4
• Molecular Mass: 705.63342
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 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 Traditional name: itraconazole
• Brand Name: Itrizole; Oriconazole; Sporal; Sporanos; Sporanox; Sporonox; Triasporn; Hyphanox
• Synonyms: 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

Database IDs

• CAS Number: 84625-61-6
• MDL Number: MFCD00865619
• PubChem SID: 160964501; 46505954
• PubChem CID: 55283
• CHEBI ID: 6076
• ATC CODE: J02AC02
• CHEMBL: 22587
• Chemspider ID: 49927
• DrugBank ID: DB01167
• KEGG ID: D00350
• Unique Ingredient Identifier: 304NUG5GF4
• Wikipedia Title: Itraconazole
• Medline Plus: a692049

CALCULATED PROPERTIES

JChem

• H Acceptors: 9
• H Donor: 0
• LogD (pH = 5.5): 7.3001556
• LogD (pH = 7.4): 7.3112283
• Log P: 7.3113713
• Molar Refractivity: 200.4 cm^3
• Polarizability: 71.596016 Å^3
• Polar Surface Area: 100.79 Å^2
• Rotatable Bonds: 11
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.48
• LOG S: -4.86
• Solubility (Water): 9.64e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Insoluble
• Apperance: White and Off-White Solid
• Melting Point: 164-166°C
• Hydrophobicity(logP): 5.99; 6.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer

Pharmacology Properties

• Admin Routes: Oral and i.v. (US), Oral only (UK)
• Bioavailability: 55%, maximal if taken with full meal
• Half Life: 21 hours
• Metabolism: hepatic (CYP3A4)
• Protein Bound: 99.8%
• Legal Status: POM (UK); Rx-only (US)
• Pregnancy Category: C (safety unknown)

Product Information

• Purity: 95%
• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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)