Novel echinocandin antifungals. Part 2: Optimization of the side chain of the natural product FR901379. Discovery of micafungin

Further optimization of the potent antifungal activity of side chain analogs of the natural product FR901379 led to the discovery of compound 8 with an excellent, well-balanced profile. Potent compounds with reduced hemolytic potential were designed based upon a disruption of the linearity of the terphenyl lipophilic side chain. The optimized compound (8, FK463, micafungin) displayed the best balance and was selected as the clinical candidate.

Graphical abstractFurther optimization of the potent antifungal activity of side chain analogs of the natural product FR901379 led to the discovery of compound 8 (micafungin) with an excellent, well-balanced profile.Figure optionsDownload full-size imageDownload as PowerPoint slide