1-(butan-2-yl)-4-{4-[4-(4-{[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: 106199
• Molecular Formular: C35H38Cl2N8O4
• Molecular Mass: 705.63342
• Monoisotopic Mass: 704.2393071
• SMILES: CCC(C)n1ncn(c1=O)c1ccc(cc1)N1CCN(CC1)c1ccc(OCC2COC(Cn3cncn3)(O2)c2ccc(Cl)cc2Cl)cc1
• Canonical SMILES: CCC(n1ncn(c1=O)c1ccc(cc1)N1CCN(CC1)c1ccc(cc1)OCC1COC(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
• InChIKey: VHVPQPYKVGDNFY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-(butan-2-yl)-4-{4-[4-(4-{[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; itraconazole
• Synonyms: Oriconazole, R51211, Sporanox; ITRACONAZOLE; Oriconazole; R51211; Sporanox; Itraconazole

Database IDs

• CAS Number: 84625-61-6
• MDL Number: MFCD00870168
• PubChem SID: 162087202
• PubChem CID: 3793

CALCULATED PROPERTIES

• 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

PROPERTIES

Physical Property

• Solubility: chloroform: soluble50 mg/mL, clear, colorless
• Melting Point: 166.0-168.0°C

Safety Information

• Storage Condition: 2-8°C
• RTECS: XZ5481000
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 3
• Risk Statements: 36/37/38; R:36/37/38
• Safety Statements: 22-26-36; S:22-26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves
• Storage Temperature: 2-8°C

Product Information

• Purity: ≥98% (TLC); 95+%
• Empirical Formula (Hill Notation): C35H38Cl2N8O4

DETAILS

Sigma Aldrich - I6657

Application
Itraconazole is a triazole antifungal agent. It is used to inhibit cytochrome P-450-dependent enzymes and ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. It′s different formulations are used to study Candida strains in murine invasive infections1. It has been used to study proliferative changes of the forestomach mucosa in alloxan-induced diabetic rats2.
Biochem/physiol Actions
Itraconazole inhibits cytochrome P-450-dependent enzymes which results in the inhibition of ergosterol synthesis. It does so by interacting with 14-α demethylase, which is a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. Ergosterol is a crucial compenent of fungal cell membranes. Therefore, it′s inhibition results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and phospholipid biosynthesis.

REFERENCES

• Chau, A.S., "Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae." Antimicrob. Agents Chemother. 50, 3917-3919, (2006)
• Xiong, Q., et al., "Cholesterol import by Aspergillus fumigatus and its influence on antifungal potency of sterol biosynthesis inhibitors." Antimicrob. Agents Chemother. 49, 518-524, (2005)
• Sabatelli, F., et al., "In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts." Antimicrob. Agents Chemother. 50, 2009-2015, (2006)
• Vanden Bossche, H., et al., "Effects of itraconazole on cytochrome P-450-dependent sterol 14α-demethylation and reduction of 3-ketosteroids in Cryptococcus neoformans." Antimicrob. Agents Chemother. 37, 2101-2105, (1993)