用人CYP转基因细胞系探索氨基氮杂环类药物的氮氧化

To study N-oxidation mechanism of five-membered azaheterocyclic drugs. Content as following: 1. Synthesis a series of matrix compounds and potential metabolites of 1-substituted 2-aminobenzimidazoles. The target compounds were purified and structures were confirmed. 2. The study were carried out on matabolic activity of these compounds by cell microsomes from human CYP transfergenic cell. 3. A HPLC method was established for separation and detection of matrix and metabolite. 4. These compounds were incubated in vitro by different microsomes. The principal types of metabolic enzymes and the metabolic path were definited. 5. The initial study on toxicology of 1-substituted 2-aminobenzimidazoles were carried out. A quantitative structure-activity relationship was developed between molecular structure and toxicity.

用人CYP转基因细胞系对1-烃基-2-氨基苯并咪唑系列化合物进行环内外氮氧化代谢的系统研究，从而明确该类化合物氮氧化代谢的酶学机理、结构改变对氮氧化位置的影响、定量结构与活性关系等。研究结果可更准确地反映此类外源化学物质对人体的毒理学作用，并为含氮新药的设计、筛选、结构改造和毒性与氮氧化途径的预测提供科学依据。