Synthesis And Biological Evaluation Of Nitrogen-containing Heterocyclic Compounds

The nitrogen-containing heterocyclic compounds play an important role in heterocyclic compounds. The heterocyclic compounds have a variety of pharmacologiacal activities in medicine, such as bactericidal, anti-inflammatory, anti-cancer. In the field of pesticide, nitrogen-containing heterocyclic compounds are widely used as insecticides, acaricides, herbicides and so on. According to the importance of nitrogen-containing heterocyclic compounds, chemist modiest nitrogen-containing heterocyclic compounds by different groups to screen out heterocyclic small molecules with better biological activity.Thiazoline and pyrazole are two important nitrogen-containing heterocyclic compounds. Thiazoline derivatives are widely used in the drug design, many natural compounds with thiazoline are demonstrated as potential anticancer drugs. Pyrazole derivatives exhibit a variety of biological activities, usually associateed with low toxicity. Up to now many chemical small molecules containing pyrazole ring have been successfully used in clinical research. Therefore the synthesis of novel thiazoline and pyrazole derivatives has the actual research significance.In this paper we discovered a new method to synthesize3-thiazoline, and with this method we synthesized a series of thiazoline hydrazone derivatives. We also used the amino acid ethyl ester modiest pyrazole derivatives, and synthesized a series of pyrazole peptide analogues. The preliminary biological activities of the products have been evaluated.This paper involves the following three parts:1. A novel route to3-thiazolineAn unexpected and novel rearrangement was discovered and used to synthesize a series of3-thiazoline derivatives. The structures of the new compounds were determined by HRMS, IR, NMR and X-ray analyses. 2. Synthesis of2-methyl-2,5-dihydrothiazole-2-carbohydrazide hydrazone derivativesBased on the obtained3-thiazoline derivatives, we synthesized a series of2-methyl-2,5-dihydrothiazole-2-carbohydrazide hydrazone derivatives. The structures of the compounds were determined by HRMS, IR, NMR and X-ray analyses.3. Synthesis and biological evaluation of1H-pyrazole-5-carboxamido derivativesThe carboxyl group in the1H-pyrazole-5-carboxylic acid derivatives was activated by the adding of EDCI, and then reacted with amino acid ethyl ester, we synthesized a series of1H-pyrazole-5-carboxamido derivatives. The structures of the compounds were determined by HRMS, IR, NMR and X-ray analyses and the preliminary biological activity evaluation of these compounds have been done. The results showed that some compounds had inhibitory effects on the growth of lung cancer A549cells and compound5e possessed the highest growth inhibitory.In summary, we have developed a novel route to synthesize3-thiazoline, and synthesized a series of2-methyl-2,5-dihydrothiazole-2-carbohydrazide hydrazone derivatives. Compared to previous studies, the reaction conditions have been further improved.We also synthesized a series of pyrazole peptide analogues and evaluated the biological activity of these compounds. This study is conducive to explore the structure-activity relationship of the drug molecules.