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  1. Alexandr XenForo Moderator

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  4. micha XenForo Moderator

    The success of azoles and polyenes in addressing a high medical need has been significant, despite their mutually exclusive limitations. Both drug classes operate by inhibiting sterol function in the fungal cell membrane, to exert an antifungal effect (see However, azoles indirectly target ergosterol function via fungal-specific inhibition of 14-sterol demethylase, to block the synthesis of functional ergosterol from nonfunctional lanosterol. No significant effect on human/mammalian cholesterol biosynthesis is achieved in vivo as a result of this activity, which underpins the mechanistic safety of azoles and As has been pointed out already, it will be important to have an azole moiety in our new antifungal; however, it should not have the 1:3-dioxolane ring system present in the structures of 23, 24, and 25, because it is expected that such a ring system might induce instability of the drug under the acidic conditions in the stomach. Thus, we wished to explore whether other oxygen-containing heterocycles represented by 26, 27, 28, 29, and 30 will possess activities of interest. We have synthesized all these novel structures with appropriate R groups in the racemic form, and determined their activities, and the results are as follows: 26, 27, and 28 were more active than 23 and 24, and, among these compounds, 27 was the most active. In this chapter we focus on the synthesis of this class of compounds that led to the discovery of posaconazole (21). In our initial studies the importance of the aromatic spacer group –OR, and the presence of an azole moiety for its broad-spectrum activity, potency, and oral bioavailability, became apparent. Fluconazole - Search Livertox Database metformin and vitamin c Fluconazole - an overview ScienceDirect Topics Fluconazole - Life
     
  5. bondagsex Guest

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  7. decil Well-Known Member

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