Novel echinocandin antifungals. Part 1: novel side-chain analogs of the natural product FR901379.
A series of novel acylated analogs of the novel water-soluble echinocandin FR901379 have been prepared and evaluated for antifungal and hemolytic activity. A relationship between antifungal activity and lipophilicity of the acyl side chain, expressed as ClogP was demonstrated, and an analog (3c) with 5.5- to 8-fold superior in vivo activity relative to the previously disclosed 4-(n-octyloxy)benzoyl side chain analog, FR131535 obtained.
Tomishima
Masaki
M
Medicinal Chemistry Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
Ohki
Hidenori
H
Yamada
Akira
A
Maki
Katsuyuki
K
Ikeda
Fumiaki
F
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D054714:Echinocandins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053878:Hemolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D054714:Echinocandins; C110368:FR 901379; D053878:Hemolytic Agents; D010456:Peptides, Cyclic