Structure–Activity Relationships of 1,3-Benzoxazole-4-carbonitriles as Novel Antifungal Agents with Potent in Vivo Efficacy

Jun-ichi Kuroyanagi; Kazuo Kanai; Takao Horiuchi; Hiroshi Takeshita; Shozo Kobayashi; Issei Achiwa; Kumi Yoshida; Koichi Nakamura; Katsuhiro Kawakami

doi:10.1248/cpb.59.341

Regular Articles

Structure–Activity Relationships of 1,3-Benzoxazole-4-carbonitriles as Novel Antifungal Agents with Potent in Vivo Efficacy

Jun-ichi Kuroyanagi, Kazuo Kanai, Takao Horiuchi, Hiroshi Takeshita, Shozo Kobayashi, Issei Achiwa, Kumi Yoshida, Koichi Nakamura, Katsuhiro Kawakami

著者情報

キーワード: 1,3-benzoxazole-4-carbonitrile, antifungal agent, physicochemical property, in vivo efficacy, bioavailability

ジャーナルフリー

2011 年 59 巻 3 号 p. 341-352

DOI https://doi.org/10.1248/cpb.59.341

詳細

抄録

A series of 1,3-benzoxazole-4-carbonitriles was synthesized and evaluated for its antifungal activity, solubility, and metabolic stability. Among those compounds, 4-cyano-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino)pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide (16b) exhibited potent in vitro activity against Candida species, higher water solubility, and improved metabolic stability compared to lead compound 1. Compound 16b showed potent in vivo efficacy against mice Candida infection models and good bioavailability in rats.

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