Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species

Novel macrocyclic amidinourea derivatives <b>11</b>, <b>18</b>, and <b>25</b> were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds <b>11</b> and <b>18</b> were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds <b>25</b> were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole