Nitrogen-containing Heterocyclic Compounds With Potential Biological Activity Study

In the research and exploitation of medicine and pestcide, hetrocyclic compounds containing nitrogen play an important role. It is a focus of the research of novel pharmaceuticals. But there are a little research on nitrogen-containing benzoheterocyclic compounds: 2,4 ?dihydro ?2 (1 H) ?keto-tetrohydroquinoxaline; I ,2.3,4-tetrahydroquino- xaline; 2,3 ?dihydro 1,4 - benzoxazine; 2,3-dihydro--benzoxazole. In fact, they play an important role in many pharmaceuticals. perhaps are their bioactivity抯 center. Therefore they maybe have potential bioactivity.The pyrimidines. whose structures are simple. exist in nature wildly. They are vital role in the research and exploitation of pharmaceuticals. The research on them is hot. Pyrimidine-cycle exists in a large number of medicines. Meantime, lots of new compounds containing pyrimidine-cycle own potential bioactivity. So it is sure to say that the pyrimidine-cycle has b ioactivity.The research of Quantitative Structure-Activity Relati- onships(QSAR), which can predicts compound抯 bioactivity, helps to know the pharmaceutical effect and design target molecular(TM). On the basis of Free-wilson model, two kinds of target molecular owning potential bioactivity are designed, as following:In order to research the synthesis of target molecular, the synthesis of nitrogen-containing benzoheterocyclic compounds has been done firstly. Compared with different synthetic methods and based on the preceding researches in our laboratory, the synthesis method of those nitrogen-containing benzoheterocyclic compounds was optimized. It is simple and direct to prepare from inexpensive and ease materials. Several derivates were prepared successfully on their properties of secondary ammonia.After 2-chloro-4, 6-disubstituted pyrimidines were prepared, in order to synthesize target molecular (One), At first, attempt to synthesize TM by nucleophilic substitution reaction between nitrogen-containing benzoheterocyclic compounds and 2-chloro-4, 6-disubstituted pyrimidines in base condition is failure. Actually, Because of the inhibiting effect of base on nucleophilic substitution reaction, heterocyclic compounds have been hydrolytic decomposition before nucleophilic substitution reaction. Banks believed that the additive of acid can decrease the rate of hytroytic reaction, has no inhibiting effect and increases the rate of nucleophilic substitution reaction. Considered the properties of materials, 8 novel target compounds were successfully synthesized in acid condition.First 2-hydroxy-4,6-di-substituted pyrimidines were synthesized,then in N, iV-dimethylacetamide(DMAC) and effect of base (K2C03) and TB IA, TM (Two) were synthesized successfully through nucleophilic substitution reaction between nitrogen containing benzoheterocyclic derivates and2-hydroxy-4,6-di-substituted pyrimidines. 8 new target compounds owning potential bioactivity were synthesizedAfter such research work, successful synthesis of 16 novel target compounds owning potential bioactivity and several interrnedia were completed.