35092-35-4Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14α-demethylase
Chai, Xiaoyun,Zhang, Jun,Hu, Honggang,Yu, Shichong,Sun, Qingyan,Dan, Zhigang,Jiang, Yuanying,Wu, Qiuye
experimental part, p. 1913 - 1920 (2009/09/30)
Based on the results of computational docking to the active site of the cytochrome P450 14α-demethylase (CYP51), a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols as analogs of fluconazole were designed, synthesized, and evaluated as antifungal agents. The MIC80 values indicate that compounds 1a-n exhibited higher activity against nearly all fungi tested except Aspergillus fumigatus than fluconazole, while compounds 2a-f, 3a-f showed no activity or only moderate activity against all fungi tested. Noticeably, the MIC value of compounds 1a, 1b and 1g is 64 times lower than that of fluconazole against Microsporum gypseum in vitro. And compounds 1a, 1b and 2b showed 128 times higher activity (with the MIC80 value of 0.0039 μg/mL) than that of fluconazole against Candida albicans and also showed higher activity than that of the other positive controls. Computational docking experiments indicated that the inhibition of CYP51 involves a coordination bond with iron of the heme group, the hydrophilic H-bonding region, the hydrophobic region, and the narrow hydrophobic cleft. In addition, the activity of the compounds would be enhanced when the side chains were shorter.
EFFECT OF NEIGHBORING PYRIDINIUM GROUPS ON THE BASIC HYDROLYSIS OF ARYLBENZOATE ESTERS
Engbersen, J. F. J.,Geurtsen, G.,Bie, D. A. De,Plas, H. C. Van Der
, p. 1795 - 1802 (2007/10/02)
Arylbenzoate esters with a quaternary pyridinium group ortho to the ester function exhibit enhanced reactivity towards basic hydrolysis relative to their para analogs in the order pyridinium 4-aminocarbonylpyridinium 3-aminocarbonylpyridinium 3-aminocarbonylquinolium.In contrast, a trimethylammonium group in the ortho position shows a decelerating effect relative to the para analog.It is concluded that the catalytic effect of a neighboring pyridinium group is based upon interaction of the negatively charged transition state of ester hydrolysis with the electron deficient ?-system of the pyridinium ring.For the p-methoxyphenolate ester containing the 3-aminocarbonylpyridinium group in the ortho position this interaction leads to a change in mechanism from rate limiting hydroxide ion attack to hydroxide ion catalyzed expulsion of the leaving group as became apparent from deviation of the Hammett plot and second-order dependence on OH(1-) concentration.For the p-nitrophenolate ester it was observed that decrease of the solvent polarity by addition of dioxane results in an increase of the rate of hydrolysis and a marked increase of the neighboring group effect.
The easy preparation of many benzylic bromides using molecular bromine as a halogenating in the presence of catalytic amounts of lanthanum tri-acetate
Ouertani, Mohsen,Girard, Pierre,Kagan, Henry B.
, p. 327 - 328 (2007/10/02)
Many benzylic brominations were easily achieved by molecular bromine in CCl4 in presence of 1 percent of La (OAc)3 and a standard room lighting lamp.The selectivity is excellent except for certain electron-rich systems (p-methylaniline, p-cresol).
