氘代策略研究抗肿瘤小分子杂环化合物的成药性

由于C-D键短于C-H键，且氘的原子量是氢2倍，C-D键的伸缩振动频率低于C-H键，致使C-D键基态能量更低，到达反应过渡态所需要的能量更高，因此，近年来制备氘代分子成为药物设计及专利保护的新策略，但尚没有系统研究氘代策略影响分子活性规律及其分子成药性规律的报道。本项目基于前期研究发现的新型高活性广谱抗肿瘤1,4-苯并二氮杂卓-2,5-二酮活性分子基础上，拟通过氘代分子的潜在代谢位点，系统研究氘代分子的构-效关系及构-代关系，并总结规律，为指导合理氘代药物设计打下基础。

The bond length of C-D is less than the C-H and deuterium has twice the atomic weight of hydrogen, the C-D bond vibrate is at a lower stretching frequency than the C-H bond, resulting in lower ground state energy and higher energy required to reach the transition state of reaction, therefore, the preparation of deuterium molecules has become a state of the art strategy for drug design and patent protection in recent years. However, there has been no systematic study and report on the impact of deuterium active compounds. Based on the previous results having found that a novel highly active broad-spectrum antitumor 1,4-benzodiazepine-2,5-diketone skeleton compounds, this project proposed a goal of deuteriation of 1,4-benzodiazepine-2,5-diketones for achievement of their antitumor druggability by investigation of structure-activity relationship and structure-metabolism relationship of active molecules via deuteriation of potential metabolic sits, and summarize regularity, lay the foundation for guiding reasonable deuterium drug design.