27656-21-9Relevant articles and documents
Structural basis for rational design of inhibitors targeting Trypanosoma cruzi Sterol 14α-demethylase: Two regions of the enzyme molecule potentiate its inhibition
Friggeri, Laura,Hargrove, Tatiana Y.,Rachakonda, Girish,Williams, Amanda D.,Wawrzak, Zdzislaw,Di Santo, Roberto,De Vita, Daniela,Waterman, Michael R.,Tortorella, Silvano,Villalta, Fernando,Lepesheva, Galina I.
, p. 6704 - 6717 (2014/09/29)
Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14α-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of β-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50 = 1.2 nM, vs (S)-2/(S)-3, EC50 = 1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.
Synthesis of dendrimer-type chiral stationary phases based on the selector of (1S,2R)-(+)-2-amino-1,2-diphenylethanol derivate and their enantioseparation evaluation by HPLC
He, Bao-Jiang,Yin, Chuan-Qi,Li, Shi-Rong,Bai, Zheng-Wu
experimental part, p. 69 - 76 (2010/09/09)
In our recent work, a series of dendritic chiral stationary phases (CSPs) were synthesized, in which the chiral selector was L-2-(p-toluenesulfonamido)-3- phenylpropionyl chloride (selector I), and the CSP derived from three-generation dendrimer showed the best separation ability. To further investigate the influence of the structures of dendrimer and chiral selector on enantioseparation ability, in this work, another series CSPs (CSPs 1-4) were prepared by immobilizing (1S,2R)-1,2-diphenyl-2-(3-phenylureido)ethyl 4-isocyanatophenylcarbamate (selector II) on one- to four-generation dendrimers that were prepared in previous work. CSPs 1 and 4 demonstrated the equivalent enantioseparation ability. CSPs 2 and 3 showed the best and poorest enantioseparation ability respectively. Basically, these two series of CSPs exhibited the equivalent enantioseparation ability although the chiral selectors were different. Considering the enantioseparation ability of the CSP derived from aminated silica gel and selector II is much better than that of the one derived from aminated silica gel and selector I, it is believed that the dendrimer conformation essentially impacts enantioseparation.
Applications of asymmetric hydrosilylations mediated by catalytic (DTBM-SEGPHOS)CuH
Lipshutz, Bruce H.,Lower, Asher,Kucejko, Robert J.,Noson, Kevin
, p. 2969 - 2972 (2007/10/03)
Several aryl ketone precursors useful in the synthesis of known physiologically active compounds have been reduced to the corresponding nonracemic alcohols. The previously reported combination of a catalytic quantity of (R)-(-)-DTBM-SEGPHOS-ligated CuH an
