title: Novel echinocandin antifungals. Part 2: Optimization of the side chain of the natural product FR901379. Discovery of micafungin.
abstract: 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.
authors.affiliation: Medicinal Chemistry Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. masaki.tomishima@jp.astellas.com
authors.forename: Masaki
authors.initials: M
authors.lastname: Tomishima
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohki
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Maki
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ikeda
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001688:Biological Products / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D054714:Echinocandins / Q000138:chemical synthesis / Q000494:pharmacology*; D055666:Lipopeptides; D008074:Lipoproteins; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D054714:Echinocandins; C110368:FR 901379; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin