Antifungal agents. 11. N-substituted derivatives of 1-[(aryl)(4-aryl-1H-pyrrol-3-yl)methyl]-1H-imidazole: Synthesis, anti-Candida activity, and QSAR studies

作者：Di Santo R^*; Tafi A; Costi R; Botta M; Artico M; Corelli F; Forte M; Caporuscio F; Angiolella L; Palamara AT

来源：Journal of Medicinal Chemistry, 2005, 48(16): 5140-5153.

DOI：10.1021/jm048997u

1-[(Aryl)(4-aryl-1H-pyrrol-3-yl)methyl]-1H-imidazoles were recently reported by our group as potent anti-Candida agents belonging to the antifungal azole class. In the present paper the synthesis, anti-Candida activities, and QSAR studies on a novel series of N-substituted 1-[(aryl)(4-aryl-1H-pyrrol-3-yl)methyl]-1H-imidazole derivatives are reported. The newly synthesized azoles were tested against 12 strains of Candida albicans together with bifonazole, miconazole, itraconazole, fluconazole, and compounds la, 1b, 3a, 3b, and 3c used as reference drugs. In general, tested derivatives showed good antifungal activities, and the most potent compound was 1d (MIC90 = 0.032,mu g/mL), which was from 4- to 250-fold more potent than reference drugs. Catalyst software was applied to develop a quantitative pharmacophore model to be used for the rational design of new antifungal azoles. Some key interactions, as well as excluded volumes, further to the coordination bond of azole antifungals with the demethylase enzyme, are highlighted.

• 出版日期2005-8-11