Synthesis Of Novel Thiazole And Thiazolidine-Containing Derivatives And Their Bioactivities Evaluation

The synthesis of nitrogen-containing heterocyclic compounds has important significance, because they display extensive biological activities, which constitute versatile building blocks for the manufacture of bioactive compounds in pharmaceutical and agrichemical industry, and has become a hot field in the medicine and pesticide research.2-Aminothiazole is an important heterocyclic framework with diverse biological activities depending on different substituent groups, which could be widely used in medicinal and pesticidal fields as lead compounds.Four series of novel2-aminothiazole compounds were designed and synthesized, and their structures were confirmed by1H NMR,13C NMR and high-resolution mass spectroscopy (HRMS). Their bioactivities were evaluated and some of the compounds exhibited good biological activities, which might be developed as potential lead compounds for further optimization.1)24compounds were designed and synthesized with2-aminothiazolidine as the core structure and the reaction condition of the key intermediate isothiacyanate was optimized. The synthesized compounds did not show any obvious biological activities to pest and bacteria, but showed good inhibitory activities against meloidogyne incongnita,12of which exhibited100%inhibition rate at the dosage of25ppm.2) Both of thiazolo[d]-oxazolidinone and imidazole-carboxylate fragments were introduced to the dihydroxyl thiazolidine compounds and22new compounds were synthesized. Target compounds presented pleasing inhibition against meloidogyne incongnita and B1、B2、B4、B5、B7exhibited100%inhibition rate at the dosage of25ppm. Besides, compounds B4and B10showed100%inhibition rate to tetranychus cinnabarinus at the dosage of500ppm.3) The dihydroxyl thiazolidine compounds were motified to improve their fat solubility.32novel compounds were synthesized and their bioassay indicated that fluorine played a positive role in promoting their activities against meloidogyne incongnita. Meanwhile, target compounds C12, C29, C19, C30showed100%mortality against armyworm (mythimna separata) at500ppm.4) A novel and practical protocol for the synthesis of fused-bicyclic2-aminothiazolyl moiety was designed by analyzing existing synthetic methods of aminothiazole compounds. The reaction condition was optimized, the effect of substituents on the structure of target compounds was studied and the mechanism of the reaction was investigated. Three series,67compounds were synthesized and their bioassay indicated that tetrahydrobenzo[d]thiazole compounds showed high inhibitory activities against meloidogyne incongnita and exhibited insectical activities. Besides, several compounds showed moderate inhibitory activities against two insect cell lines (S2and Sf9) and two mammalian cell lines (Hela and293).5) Target compounds were screened for their interaction with andrgen receptor (AR) using yeast two-hybrid system. The screen result showed that three of2-arylimino-4-phenylthiazole compounds C8、C15、C18and most of tetrahydro-benzo[d]thiazole compounds exhibited excellent inhibitory activities against AR. Among them, D8、D13、D33、D35and D45rivaled widely used antiandrogenic prostate cancer drugs flutamide at the molecular level. Mode of action research by molecular docking indicated that active compounds binded to both AF2and BF3domains. In these two domains, fused-bicyclic thiazolyl moiety was well fitted into the non-polar hydrophobic pockets of the ligand binding sites, lead to the forming of cation-π interaction with Lys72or edge to face π-π interaction with Phe826and Pro723, with enhancing binding affinity of molecular to ligand. Tetrahydrobenzo[d]-thiazole compounds might be developed as novel lead moleculars of nonsteroidal androgen receptor antagonist.