To discover potential sterol 14α-demethylase (CYP51) inhibitors, thirty-four unreported 4H-pyrano[3,2-c]pyridine derivatives were designed and synthesized. The assay results indicated that most compounds displayed significant fungicidal activity against Sclerotinia sclerotiorum, Colletotrichum lagenarium, Botrytis cinerea, Penicillium digitatum, and Fusarium oxysporum at 16 μg/mL. The half maximal effective concentration (EC₅₀) values of compounds 7a, 7b, and 7f against B. cinerea were 0.326, 0.530, and 0.610, respectively. Namely, they had better antifungal activity than epoxiconazole (EC₅₀ = 0.670 μg/mL). Meanwhile, their half maximal inhibitory concentration (IC₅₀) values against CYP51 were 0.377, 0.611, and 0.748 μg/mL, respectively, representing that they also possessed better inhibitory activities than epoxiconazole (IC₅₀ = 0.802 μg/mL). The fluorescent quenching tests of proteins showed that 7a and 7b had similar quenching patterns to epoxiconazole. The molecular dynamics simulations indicated that the binding free energy of 7a and epoxiconazole to CYP51 was −35.4 and −27.6 kcal/mol, respectively.

中文翻译：

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作为潜在甾醇 14α-脱甲基酶 (CYP51) 抑制剂的新型 4H-吡喃并[3,2-c]吡啶类似物的设计、合成、生物活性评价和分子动力学模拟


为了发现潜在的甾醇 14α-去甲基酶 (CYP51) 抑制剂，设计并合成了 34 种未报道的 4H-吡喃并[3,2-c]吡啶衍生物。测定结果表明，大多数化合物在 16 μg/mL 浓度下对核盘菌、炭疽菌、灰葡萄孢、指状青霉和尖孢镰刀菌表现出显着的杀菌活性。化合物7a、7b和7f对抗灰霉病的半数最大有效浓度(EC ₅₀ )值分别为0.326、0.530和0.610。即，它们比氧环唑具有更好的抗真菌活性（EC ₅₀ = 0.670 μg/mL）。同时，它们对CYP51的半数抑制浓度（IC ₅₀ ）值分别为0.377、0.611和0.748 μg/mL，表明它们也比氧环唑（IC ₅₀