Synthesis And Biological Activity Of N-2-Perfluoroalkylethyl-substituted Or Glucopyranosyl-substituted Triazole Derivatives

Triazole derivatives have received considerable attention among medicinal chemists because molecules with these structural features have been found to display a wide range of potent biological activities, such as antifungal, antihypertensive, antibacterial, analgesic, anti-inflammatory, coccidiostatic, antiviral, tuberculostatic, anticonvulsion, controgestational and antitumoral. Recently, fluorinated functional compounds have been gained to chemist's attentions since it was found that the introduction of fluorine atoms or fluorous alkyl into organic molecules could lead to significant changes in biological activities. Many papers have reported the reactivity of the hydrogen of NH group in heterocycle, for example, Mannich base reaction. However, the same hydrogen substituted by perfluoroalkyl is not reported in the literature besides our research group. Compound 3 was synthesized by reaction of acid chloride with amino acid ester in the presence of Et3N and DMF. After several steps synthesizing, the 1,2,4-triazole-5-thiones (6a~6f) were obtained. Combining the perfluoroalkyl and triazole with good activities, a series of N-2-perfluoroalkyl- ethyl-substituted 1,2,4-triazole-5-thiones (7a~7l) were synthesized in the second chapter in this paper and their structures were confirmed by 1H-NMR, 19F-NMR, IR, mass spectra and elemental analysis. Their biological activities are being tested.The third chapter in the present paper focuses on the synthesis of 1,2,4-triazole Schiff bases, in other words, the research work is the continuation of the second chapter. It was reported that the 1,2,4-triazole Schiff bases which were obtained by the reaction of 1,2,4-triazole with aldehydes also have a wide range of biological activities. The different biological activity functional group to gather in the identical molecule can realize the active superimposition and develop newly highly-efficient heterocyclic compounds with broad-spectrum activity. Accordingly, the 1,2,4-triazole-5-thione Schiff bases were synthesized by the reaction of some different substituted aromatic aldehydes with 1,2,4-triazole. Then, the hydrogen of NH group in heterocycle was substituted by perfluoroalkyl iodides and 26 new target compounds were obtained (11a~11i, 12a~12i, 16a~16d and 17a~17d). The results of preliminary bioassay showed that some target compounds possessed obvious insecticidal activity. Carbohydrates are a large group of biomolecules which are distributed widely in nature and involved in a great variety of physiological and pathological processes. Sugar modification can decrease the toxicity and increase absorption of some nature drugs. Nowadays, synthesis of sugar compounds to modify nature drugs has become an important field of pharmaceutical chemistry. In order to decrease toxicities of the 1,2,4-triazole Schiff bases and enhance pharmacal effects and gain the relative derivatives with better curing effect and selectivity, structures of the Schiff bases were modified by inducing glycosyl groups in the fourth chapter in this paper. Four glycopyranosyl-substituted 1,2,4-triazole-5-thione Schiff bases (18a~18d) were synthesized and not reported in literatures until now. The results of preliminary bioassay showed that these target compounds possessed obvious insecticidal activity and antitumor activity.