posaconazole

Introduction                                            

Posaconazole is a broad-spectrum triazole active against various yeasts and molds, including Aspergillus, Candida, Fusarium, and Zygomycetes. Posaconazole inhibits the growth of fungi by inhibiting the lanosterol 14α-demethylase enzyme (IC50s range from 7-200 nM), which results in a disruption the synthesis of ergosterol, a key sterol necessary for fungal cell membrane integrity and for the function of certain membrane-bound proteins.Posaconazole is a broad-spectrum, second generation, triazole compound with antifungal activity. Posaconazole strongly inhibits 14-alpha demethylase, a cytochrome P450-dependent enzyme. Posaconazole is a sterol C14a demethylase inhibitor with an IC50 of 0.25 nM. Inhibition of 14-alpha-demethylase prevents the conversion of lanosterol to ergosterol, an important component of the fungal cell wall. Inhibition of ergosterol synthesis changes the fungal cell membrane composition and integrity, alters membrane permeability and eventually leads to fungal cell lysis. Compared to other azole antifungals, posaconazole is a significantly more potent inhibitor of sterol 14-alpha demethylase. Posaconazole is the most advanced candidate for the treatment of Chagas disease. Posaconazole has entered in a phase II clinical trial in the treatment of mycoses.     

Function                                                  

Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.

Application                                             

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Specification