Synthesis and antifungal activity of a series of novel 1,2-disubstituted propenones.
To find an antifungal agent other than those of the imidazole and triazole series, a new class of 1,2-disubstituted propenones I and II was prepared and tested for antifungal activity. Comparison of the structure-activity relationships showed that the conjugated structure of carbonyl and exomethylene groups in I and II plays an important role in potent antifungal activity. However, it is noteworthy that compounds 53, 54, and 56, which have a hydroxymethyl or methoxymethyl group instead of an exo-methylene group in I, also showed potent activity. Although many compounds exhibited strong antifungal activity in vitro, none showed activity in vivo of oral efficacy against subacute systemic candidiasis in mice.
Ogata
M
M
Matsumoto
H
H
Kida
S
S
Shimizu
S
S
Tawara
K
K
Kawamura
Y
Y
D000818:Animals; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D005658:Fungi / Q000187:drug effects*; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D011427:Propiophenones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014249:Trichophyton / Q000187:drug effects
D007659:Ketones; D011427:Propiophenones