Synthesis And Biological Activities Of 5-(Alkylamino)imidazolidine-2, 4-dione Derivatives

Since the finding of hydantoin in human bronchial epithelial cells in nineteenth century, hydantoin and its derivatives have been drawing great attention for their bioactivity and possibility as drug application. In 1985, after the last review on the chemistry of hydantoins published by Lopez and Trigo, some new findings in chemistry of hydantoin derivatives and their bioactivity have appeared and some of them have been actually used in clinic. Beside the traditional usage, for example, phenytoin has been used as the drug for antiepileptic treatment, azimilide as an antiarrhythmic, nitrofurantoin as an antibacterial substance and dantrium as a sceletal muscle relaxant, etc., hydantoins have also been developed as new drugs in the treatment of other diseases, such as nilutamide, which was approved by the FDA in 1996 as a nonsteroidal, orally active antiandrogen in the therapy of metastatic prostate cancer.Thereby, more and more chemists focus on the synthesis of hydantoins. New synthetic methods and new derivatires of hydantoin have been developed. According to the results we obtained from the homology modeling of D1 protease in PSII center and the subsequent virtual screening of lead compounds, hydantoin derivatives with amino group at 5 position were selected as a kind of lead compounds and them have not been reported before accoding to our knowledge. Therefore, this thesis will focus on the rational design and synthesis of this kind of 5-substitued amino hydantoin derivatives and it is expected that this kind of lead compounds may have special herbicidal activity.D1 protease (CptA) is absolutely necessary in photosynthesis of plant. CptA was regard as an excellent potential target of herbicide in the plant photosynthesis II. Because the number of the CptA has only 1% of the number of D1 protein, it is expected the inhibitors to CptA will have great advantages over the common used D1 protein inhibitors, such as Simagine, Atrazine, Diuron, etc.Based on the results from the homology modeling and virtual screening, we designed and synthesized a series of 5-(alkylamino)imidazolidine-2,4-dione Derivatives , and their bioactivities were tested. Furthermore, one of the target compounds was immobilized at the interface of a SPR biosensor, and its interaction with D1 protease was investigated. The main work of this paper contains:1. Three new 5-(Alkylamino)imidazolidine-2,4-diones were synthesized by using the intermediate of imidazolidine-2,4,5-trione, and their molecular structures were confirmed by NMR, GC-MS, IR, etc.2. By acylation of the exocyclic amino group of the corresponding 5-(Alkylamino)imidazolidine-2,4-diones, the I compounds of the following scheme were obtained; and By acylation of the exocyclic amino group and the third amino group of the endocyclic of the corresponding 5-(Alkylamino)imidazolidine-2,4-diones, the II compounds of the following scheme were obtained. Their molecular structures were confirmed by by NMR, GC-MS, IR, etc.3. All of the new compounds were researched the active of biology. Most of the compounds can control on the growth of rape in 100ppm, the rate of growth controlling of the compound are above 80%. The rate of growth controlling of the II compounds of the following scheme are above 90%.4. One of the new compounds that contain dithiolane was researched the surface plasma resonance with CtpA of spinach. We found that this new compound clearly act with the CtpA of spinach, k_a = 3.94×10³ M^-1S^-1, K_A = 5.59×10⁶M^-1.