Itraconazole structure

Other fluoroazoles are emerging flutrimazole (for topical treatment) and voriconazole, which has a good diffusion in cephalorachidian liquid. Posoconazole (Phase III) is the fluoro analogue of itraconazole. The structural complexity (four chiral centers) of posoconazole is remarkable (Figure S.23). Albaconazole, CS-758, Syn-2869, and Azoline have the same structural core as voriconazole they are in the early stage of clinical development. ... 

Atypical Spherazole CR system is a tablet that consists of a sandwiched structure as shown in Figure 22.14. Such a system was prepared by the following procedures The water-insoluble drug itraconazole is layered onto microcrystalline cellulose with Eudragit E100 as a binder to form... 

A unit of the x-ray structure (13.12) of a cocrystal between itraconazole and succinic acid (HO2CCH2CH2CO2H), is shown in Figure 13.6. The cocrystal involves two molecules of itraconazole encapsulating a single succinic acid molecule. The OH groups of the acid form a hydrogen... 

FIGURE 13.6 X-ray structure of an itraconazole-succinic acid cocrystal. Published with permission from Remenar, J. F., et a. J.Am. Chem.Soc. 2003, 125,8456-8457. Copyright 2003 American Chemical Society. 

Posaconazole is similar in structure to itraconazole. It was well tolerated and as effective as fluconazole 100 mg in two large randomized comparisons in HIV-infected patients with oropharyngeal candidiasis. In a salvage study in patients with a variety of invasive fungal infections, there were response rates of 44-80% in patients with aspergillosis, fusariosis, cryptococcosis, candidiasis, and pheohyphomycoses after 4-8 weeks of therapy (1,2). 

Saperconazole is an experimental, water-insoluble, lipophilic, fluorinated triazole. Its structure resembles that of itraconazole and it has a long half-life. It has a broad antifungal spectrum, including Cryptococcus Species and Aspergillus species. In early studies in cases of compassionate use, only a few adverse effects were described, including hepatotoxicity (1,2), and its adverse effects were expected to resemble those of itraconazole (3). However, the manufacturers stopped developing it because of concerns about toxicity. 

Itraconazole, USP. 4- 4- 4- 4- 2-(2,4-Diehlorophe-nyl)-2-l//-l.2.4-tria/.ol-l-ylmethyl)-l.3-dioxolan4-yl mcth-oxy I phenyl -1 -pipera/iny I (phenyl -2.4-dihydro-2-( I - nieth-ylpropyl)-3//-l.2.4-tria zol-3-onc (Sporanox) is a unique member of the azole class that contains two triazole moieties in its structure, a weakly ba.sic 1.2.4-triaznlc and a nonbasic 1,2,4-tria/ol-3-one. 

Fig. 4.3 Structures of polyene (amphotericin B) and azole (itraconazole, fluconazole, miconazole and ketoconazole) antifungal agents.

Itraconazole. Itraconazole (18) is a highly lipophilic compound with a triazole structure. Compared to ketoconazole, itraconazole has a broader spectrum (including Aspergillus spp.) (29,30) and an in vitro activity that is 10 times higher than ketoconazole for most species. 

CYP51F1 Saccharomyces cerevi-siae YJM789 4LXJ, 4KOF Lanosterol, itraconazole Lanosterol 14a-demethylase, full length structure with membrane-spanning helix [467]... 

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