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Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2

2002; Elsevier BV; Volume: 12; Issue: 4 Linguagem: Inglês

10.1016/s0960-894x(01)00808-3

1464-3405

Hirosato Ebiike, Miyako Masubuchi, Pingli Liu, Ken‐ichi Kawasaki, Kenji Morikami, Satoshi Sogabe, Michiko Hayase, Toshihiko Fujii, Kiyoaki Sakata, Hidetoshi Shindoh, Yasuhiko Shiratori, Yuko Aoki, Tatsuo Ohtsuka, Nobuo Shimma,

Synthesis and biological activity

Modification of the C-2 position of a benzofuran derivative 6 (RO-09-4609), an N-myristoyltransferase (Nmt) inhibitor, has led us to discover antifungal agents that are active in a murine systemic candidiasis model. The drug design is based on the analysis of a crystal structure of a Candida Nmt complex with 2. The optimization has been guided by various biological evaluations including a quasi in vivo assay and pharmacokinetic analysis.