title: 1,3-Benzoxazole-4-carbonitrile as a novel antifungal scaffold of β-1,6-glucan synthesis inhibitors.
abstract: Synthesis and in vitro antifungal evaluations of 1,3-benzoxazole-7-carbonitrile 3, 1,3-benzoxazole-4-carbonitrile 4, benzofuran 5, benzoxazine 7, and benzimidazole 8 were reported. Among them, 1,3-benzoxazole-4-carbonitrile was found to be a superior scaffold structure with moderate growth inhibition against Candida species. 1,3-Benzoxazole-4-carbonitrile 6 showed potent activity against Candida species compared to 5-desmethyl compound 4 and triazolopyridine 2. Compound 6 was efficiently prepared from versatile intermediate 24, which possessed six different substituents on the benzene ring. Conversion of benzene 24 into various 1,3-benzoxazole derivatives such as 2-aliphatic 34, 2-amino 35, and lactone 38 was demonstrated.
authors.affiliation: Lead Discovery & Optimization Research Laboratories II, Daiichi Sankyo Co., Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. kuroyanagi.junichi.d5@daiichisankyo.co.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kuroyanagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kanai
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Takao
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Issei
authors.initials: I
authors.lastname: Achiwa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002175:Candida / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D047071:beta-Glucans / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D009570:Nitriles; D047071:beta-Glucans; C064197:beta-1,6-glucan; C031000:benzimidazole