Author/Authors :
Hirosato Ebiike، نويسنده , , Miyako Masubuchi، نويسنده , , Pingli Liu، نويسنده , , Ken-ichi Kawasaki، نويسنده , , Kenji Morikami، نويسنده , , Satoshi Sogabe، نويسنده , , Michiko Hayase، نويسنده , , Toshihiko Fujii، نويسنده , , Kiyoaki Sakata، نويسنده , , Hidetoshi Shindoh، نويسنده , , Yasuhiko Shiratori، نويسنده , , Yuko Aoki، نويسنده , , Tatsuo Ohtsuka، نويسنده , , Nobuo Shimma، نويسنده ,
Abstract :
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.
