Novel pyridobenzimidazole derivatives exhibiting antifungal activity by the inhibition of beta-1,6-glucan synthesis.
Based on the HTS hit compound 1a, an inhibitor of beta-1,6-glucan synthesis, we synthesized novel pyridobenzimidazole derivatives and evaluated their antifungal activity. Among the compounds synthesized, we identified the potent compound 15e, which exhibits excellent activity superior to fluconazole against both Candida glabrata and Candida krusei. From the SAR study, we revealed essential moieties for antifungal activity.
Takeshita
Hiroshi
H
Daiichi Sankyo Co., Ltd, Kitakasai, Edogawa-ku, Tokyo, Japan. takeshita.hiroshi.km@daiichisankyo.co.jp
Watanabe
Jun
J
Kimura
Yoichi
Y
Kawakami
Katsuhiro
K
Takahashi
Hisashi
H
Takemura
Makoto
M
Kitamura
Akihiro
A
Someya
Kazuhiko
K
Nakajima
Ryohei
R
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D047071:beta-Glucans / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000935:Antifungal Agents; D001562:Benzimidazoles; D047071:beta-Glucans; C064197:beta-1,6-glucan