Chemical and biological aspects of posaconazole as a classic antifungal agent with non-classical properties: highlighting a tetrahydrofuran-based drug toward generation of new drugs

Posaconazole (PSZ, SCH 56592), is a new generation of orally active triazole antifungal agent with a tetrahydrofuran center, derived from itraconazole (ITZ). This drug has a broader spectrum of activity respect to the dioxolane-based triazoles. Structurally, PSZ molecule with four chiral centers and long side chain has a complicated structure. In this review, we describe general aspects of PSZ, including chemistry, pharmacological properties, mechanism of action, synthetic strategies, synthesis of key intermediates, structure-antifungal activity relationships, and the design of its prodrugs. Finally, the non-classical properties of PSZ including antitrypanosomal, antileishmanial and hedgehog (Hh) signaling pathway inhibitory activities will be discussed. By highlighting the information and experiences gained with PSZ, we can better move toward newer compounds of this generation. [GRAPHICS] .

Automated summary

Posaconazole is a broad-spectrum oral antifungal drug with a complex structure. Its non-classical properties make it have antitrypanosomal, antileishmanial, and hedgehog signaling pathway inhibitory activities.