A Convenient Synthesis, Reactions and Biological Activity of Some New 6H-Pyrazolo[4',3':4,5]thieno[3,2-d][1,2,3]triazine Compounds as Antibacterial, Anti-Fungal and Anti-Inflammatory Agents

We describe here the design and synthesis of novel pyrazolothienotriazine compounds based on diazotization followed by cycloaddition reactions of 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazol-5-carbonitrile with sodium nitrite in the presence of concentrated HCl in acetic acid. The produced chloropyrazolothienotriazine underwent nucleophilic substitution reactions with various primary and secondary amines including sulfa drugs to afford the N-substituted aminopyrazolothienotriazines. Hydrazinolysis of the chlorotriazine with hydrazine hydrate afforded the hydrazinotriazine, which was used as a versatile precursor for synthesis of other compounds. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing Fourier transform infrared spectroscopy (FTIR),1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry. Some of the synthesized compounds showed high antibacterial and anti-fungal activities. Also, most of the tested compounds exhibited high anti-inflammatory activity compared with indomethacin using carrageenan induced rat paw edema assay.

本文阐述了新型吡唑并噻吩并三嗪类化合物的设计与合成方法：以4-氨基-3-甲基-1-苯基-1H-噻吩并[2,3-c]吡唑-5-甲腈为原料，在乙酸体系中的浓盐酸存在下与亚硝酸钠发生重氮化-环加成串联反应。所制得的氯代吡唑并噻吩并三嗪可与包括磺胺类药物在内的多种伯胺、仲胺发生亲核取代反应，得到N-取代氨基吡唑并噻吩并三嗪类化合物。通过水合肼对该氯代三嗪进行肼解反应，可得到肼基三嗪，后者可作为合成其他化合物的多用途前体。新合成化合物的化学结构通过元素分析及光谱分析得以确证，所用光谱技术包括傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）、1H及13C核磁共振波谱（nuclear magnetic resonance，NMR）以及质谱法。部分合成化合物表现出优异的抗菌与抗真菌活性；此外，与对照药物吲哚美辛相比，多数受试化合物在角叉菜胶诱导的大鼠足肿胀实验中展现出较高的抗炎活性。