Skrzypczak-Jankun E, Kurumbail R G
Department of Chemistry, University of Toledo, OH 43606, USA.
Acta Crystallogr C. 1996 Jan 15;52 ( Pt 1):189-91. doi: 10.1107/s0108270195010183.
X-ray analysis confirmed the configuration of the title N1-alkylated C4-nitroimidazole inhibitor. The plane of the imidazole ring, sitting on an axis of the trityl propeller, bisects the angle between two phenyl rings, while the nitro group extends over the third. Modeling of the interactions between the cytochrome P450 and the title compound (C22H17N3O2) has been performed on the basis of the crystal structures of 1-trityl-4-nitroimidazole and bacterial cytochrome P450BM-3. The replacements and deletions in the sequence of the latter has been performed to match mammalian cytochrome P450-IIIA1. The modeling explained why inhibitors with a C4-substituted imidazole ring showed lower effectivity than those without substituents, as an additional group of atoms at C4 prevents close interactions of the imidazole ring with the heme Fe atom.
X射线分析确定了标题中N1-烷基化C4-硝基咪唑抑制剂的结构。咪唑环平面位于三苯甲基螺旋桨轴上，将两个苯环之间的夹角平分，而硝基则伸向第三个苯环。基于1-三苯甲基-4-硝基咪唑和细菌细胞色素P450BM-3的晶体结构，对细胞色素P450与标题化合物（C22H17N3O2）之间的相互作用进行了建模。对后者的序列进行了替换和删除，以匹配哺乳动物细胞色素P450-IIIA1。该建模解释了为什么具有C4-取代咪唑环的抑制剂比没有取代基的抑制剂效果更低，因为C4处的额外原子基团会阻止咪唑环与血红素铁原子的紧密相互作用。
