The synthesis of nitrogen-containing heterocyclic compounds is of great significance, because such compounds have a wide range of biological activities and are important synthetic building blocks for the construction of biologically active compounds. They are also a hot area in the research of pharmaceutical intermediates and pesticides. 2-Aminothiazole is one of the typical representatives. When the substituents on the thiazole ring change, they will show different biological activities, and can be used not only as a pesticide leader, but also as a pharmaceutical leader. In this paper, four types of 2-aminothiazole compounds with brand-new structures were designed and synthesized, and the structures were confirmed by hydrogen nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), and high resolution mass spectrometry (HRMS). The synthesis and biological activity of 2-aminothiazole were systematically studied, and the results showed that some compounds showed better biological properties and are expected to become new leaders for further structural derivation.

1) The first step to study the synthesis and biological activity of 2-aminothiazole is to use 2-aminothiazolidine as the core structure, design and synthesize 24 target compounds, and optimize the synthesis of the important reaction intermediate isothiocyanate . The activity test showed that the target compound did not show obvious biological activity to pests and diseases, but had good nematicidal activity. There are 12 compounds that have a 100% lethality to nematodes at a concentration of 25ppm.

2) Among the four types of 2-aminothiazole compounds with brand-new structures, there are two structural fragments of thiazolooxazolidinone and imidazolecarboxylate introduced at the same time with the synthesized bishydroxy 2-aminothiazolidine compound as the leader. Synthesized 22 target compounds that have not been reported in the literature. The biological activity test found that most of the target compounds exhibited relatively good inhibitory activity against nematodes. Among them, the lethality rate of B1, B2, B4, B5, and B7 at a concentration of 25ppm can reach 100%. In addition, compounds B4 and B10 are resistant to nematodes at a concentration of 500ppm. Tetranychus cinnabarinus has a fatality rate of 100%.

3) The polyhydroxythiazolidine compound has been modified to improve its fat solubility, and 32 2-arylimino-4-phenylthiazole target compounds have been designed and synthesized. The biological activity test results show that most of the target compounds are Nematodes have a certain inhibitory activity, and fluorine atoms have a promoting effect on the increase of activity; in addition, compounds C12, C29, C19, and C30 show 100% lethality to Mythimna separata at a concentration of 500ppm.
4) Since this kind of research is a hotspot in the research of pharmaceutical intermediates and pesticides, from the perspective of innovation, by analyzing the synthesis and biological activity of the existing 2-aminothiazole, a novel synthetic route of 2-aminothiazole was designed, and The reaction conditions were optimized, the reaction substrates were expanded, and the reaction mechanism was initially explored. A total of 67 2-aminocycloalkylthiazole compounds that have not been reported in the literature were synthesized in three categories. The biological activity test results showed that most of the six-membered ring target compounds exhibited relatively good inhibitory activity against nematodes, and also showed a certain degree of killing. Activity of Mythimna separata and Nilaparvata lugens. Cytotoxicity tests showed that the target compound has a certain inhibitory effect on two types of insect cells (S2 and Sf9) and two types of mammalian cells (HeLa and 293).

5) Using yeast two-hybrid system to screen the role of the synthesized target compound and androgen receptor (AR). The results showed that the target compounds C8, C15, C18 and most of the tetrahydrobenzothiazole compounds with 2-arylimino-4-phenylthiazole structure showed strong antagonism to AR, among which 8, D13 The ability of D33, D35 and D45 to inhibit AR activity at the molecular level is close to or better than the positive control flutamide. The mode of action of the compound was studied by molecular docking, and the results showed that the active compound can act on the AF2 and BF3 regions at the same time. In these two regions, the merging part of the compound can dock well into the non-polar hydrophobic pocket of the ligand binding site, and form cation-π with Lys720 or form "edge-to-side" with Phe826 and Pro723. The π-π interaction enhances the binding ability between the compound and AR. Tetrahydrobenzothiazole compounds are expected to become new leaders of non-steroidal androgen receptor antagonists. Through the research on the synthesis and biological activity of 2-aminothiazole, the effective information for this kind research of pharmaceutical intermediates and pesticides is more perfect, and the four types of 2-aminothiazole compounds with brand-new structures designed and synthesized in this paper can also be used in the future. Do effective information guidance for the research.

Tags: Research of pharmaceutical intermediates and pesticides, Synthesis and biological activity of 2-aminothiazole, 2-aminothiazole compounds with brand-new structures