Previously, 2-alkylchromans have been introduced as non-azole inhibitors of 14a-demethylase. Accordingly, we incorporated imidazole ring on the 3-position of 2-alkylchromanones to design new inhibitors of 14a-demethylase and potential antifungal agents. Thus, a series of 2-alkyl-3-imidazolylchromanones were synthesized starting from 2-hydroxyphenacyl bromide. The transconfiguration of compounds was confirmed by NMR-spectroscopy. The antifungal activity of title compounds were evaluated against different fungi in comparison with fluconazole and miconazole. trans-2-(1-Pentyl)-3-imidazolylchroman-4-one (4d) showed the most potent activity against yeasts comparable to fluconazole. The experimental data based on 1 H NMR spectroscopy revealed that 2-alkyl side chain and 3-imidazolyl moiety in compound 4d exist predominantly in the di-equatorial conformation. While docking study with 14a-demethylase demonstrated that the di-axial form of compound 4d can be considered as active conformation.