Structure-activity relationships of 1,3-benzoxazole-4-carbonitriles as novel antifungal agents with potent in vivo efficacy.

Abstract

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.

• Authors: Jun-ichi Kuroyanagi, Kazuo Kanai, Takao Horiuchi, Hiroshi Takeshita, Shozo Kobayashi, Issei Achiwa, Kumi Yoshida, Koichi Nakamura, Katsuhiro Kawakami
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 59 Issue 3 Pg. 341-52 ( 2011) ISSN: 1347-5223 [Electronic] Japan
• PMID: 21372416 (Publication Type: Journal Article)

Chemical References

• 4-cyano-N,N,5-trimethyl-7-((3S)-3-methyl-3-(methylamino) pyrrolidin-1-yl)-6-phenyl-1,3-benzoxazole-2-carboxamide
• Antifungal Agents
• Benzoxazoles
• Nitriles

Topics

• Animals
• Antifungal Agents (chemical synthesis, chemistry, therapeutic use)
• Benzoxazoles (chemical synthesis, chemistry, therapeutic use)
• Candida (drug effects)
• Candidiasis (drug therapy)
• Mice
• Microbial Sensitivity Tests
• Nitriles (chemical synthesis, chemistry, therapeutic use)
• Rats
• Solubility
• Structure-Activity Relationship