title: Novel pyridobenzimidazole derivatives exhibiting antifungal activity by the inhibition of beta-1,6-glucan synthesis.
abstract: 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.
authors.affiliation: Daiichi Sankyo Co., Ltd, Kitakasai, Edogawa-ku, Tokyo, Japan. takeshita.hiroshi.km@daiichisankyo.co.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kawakami
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Takemura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kitamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Someya
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nakajima
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D001562:Benzimidazoles; D047071:beta-Glucans; C064197:beta-1,6-glucan