5245. Itraconazole

Nomenclature

CAS number: 84625-61-6
4-[4-[4-[4-[[2-(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; (±)-1-sec-butyl-4-[p-[4-[p-[[(2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-Δ2-1,2,4-triazolin-5-one; oriconazole; R-51211; Itrizole (J & J); Sempera (Janssen-Cilag); Siros (Janssen-Cilag); Sporanox (Janssen-Cilag); Triasporin (Italfarmaco).
C35H38Cl2N8O4; mol wt 705.63.
C 59.57%, H 5.43%, Cl 10.05%, N 15.88%, O 9.07%.

Description and references

Orally active antimycotic structurally related to ketoconazole, q.v. Prepn: J. Heeres, L. J. J. Backx, EP 6711; eidem, US 4267179 (1980, 1981 both to Janssen); J. Heeres et al., J. Med. Chem. 27, 894 (1984). In vitro activity: A. Espinel-Ingroff et al., Antimicrob. Agents Chemother. 26, 5 (1984). HPLC determn in biological samples: R. Woestenborghs et al., J. Chromatogr. 413, 332 (1987). Symposium on pharmacology and clinical efficacy: Rev. Infect. Dis. 9, Suppl 1, S1-S152 (1987). Toxicity data: H. Van Cauteren et al., ibid. S43. Review of clinical pharmacokinetics: J. Heykants et al., Mycoses 32, Suppl 1, 67-87 (1989); A. G. Prentice, A. Glasmacher, J. Antimicrob. Chemother. 56, i17-i22 (2005); of clinical efficacy in dermatophytosis: P. De Doncker, G. Cauwenbergh, Br. J. Clin. Pract. Suppl. 71, 118-122 (1990). Review: A. M. Sugar, Curr. Clin. Top. Infect. Dis. 13, 74-98 (1993); R. Caputo, Expert Rev. Anti Infect. Ther. 1, 531-542 (2003).

Chemical structure

Properties

Crystals from toluene, mp 166.2°. pKa 3.7. Lipophilic; partition coefficient (n-octanol/aq buffer of pH 8.1): 5.66. Practically insol in water and dil acidic solns. LD50 (14 day) in mice, rats, dogs (mg/kg): >320, >320, >200 orally (Van Cauteren).

Therapeutic Category

Antifungal.

Therapeutic Category (Veterinary)

Antifungal.

Keywords

Antifungal (Synthetic); Triazoles