取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

Synthesis, Structure and Biological Activities of Substituted Pyrazol-5-yl-carbonyl-heterocycles

为了寻求新的含吡唑双杂环先导化合物.用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物.化合物结构用IR,1H NMR,MS和元素分析进行了表征.并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构.晶体为单斜晶系,P21/n(#14)空间群,a=1.52175(3)nm,b=0.52970(1)nm,c=1.58185(3)nm,β=104.893(4)°,V=1.2323(4)nm3,Z=4,Dc=1.45g/cm3,F(000)=560.00,R1=0.064,wR2=0.193.初步生物活性实验结果表明,在25mg/L浓度下,3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c),3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%.在500mg/L浓度下,3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d),3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cincticeps)的抑制活性达到53.37%.

In order to find new pyrazol-5-yl-carbonyl-heterocycles lead compounds, 12 pyrazolylheterocycles were synthesized from 3-ethyl-1-methyl-4-substitute-5- pyrazolecarboxylic acid chloride and nitrogen heterocyclic compounds such as 2-thiazolidone, 2-thiazolidinone, 2-oxazolidinone, etc. The structures of compounds obtained were confirmed by ^1H NMR, IR, MS spectra and elemental analysis. The crystal structure of 3-（3-ethyl-l-methyl-4-nitro-1H-pyrazol-5-yl-carbonyl）oxazolidin-2-one （3k） was determined by X-ray diffraction analysis. 3k belongs to the monoclinic system with space group P21/n （#14） and cell dimensions： α=1.52175（3） nm, b=0.52970（1） nm, c= 1.58185（3） nm, β= 104.893（4）°, V= 1.2323（4） nm^3, Z=4, Dc=1.45 g/cm^3, F（000）=560.00, R1=0.064, ωR2=0.193. The results of biological tests indicated that, at 25 mg/L, 3-（3-ethyl- 1-methyl-4-nitro- 1H-pyrazole-5-carbonyl）thiazolidin-2-one （3c） and 3-（3-ethyl-1-methyl-4-nitro-1H-pyrazole-5-carbonyl）-2-thiono-thiazolidine （3g） showed inhibitory activities of 40% against Pyricularia oryzae. At 500 mg/L, 3-（3-ethyl- 1-methyl-4-bromo-1H-pyrazol-5-yl-carbonyl）thiazolidin-2-one （3d） and 3-（3-ethyl-l-methyl-4-bromo-1H-pyrazol-5-yl-carbonyl）oxazolidin-2-one （31） showed inhibitory activities of 53.37% against Nephotettix cincticeps.