新型吡唑酰腙类化合物的合成及其生物活性

Synthesis and Biological Activities of Novel Acylhydrazone Compounds Containing Pyrazole Group

以取代肼和取代乙酰乙酸乙酯为起始原料,依次经闭环、氯酰化、氧化、酯化及取代反应制得1,3-取代-5-氯-4-吡唑甲酰肼(7a,7d,7g和7j);7分别与取代呋喃或噻吩甲醛经加成反应合成了12个新型的吡唑酰腙类化合物(9a^9l),其结构经1H NMR,13C NMR,IR和元素分析表征。初步的生物活性测试结果表明:在500μg·m L-1浓度下,部分化合物对烟草花叶病毒(TMV)具有一定的抑制活性,其中1-苯基-3-三氟甲基-5-氯-4-(2-噻吩)-腙基羰基吡唑(9k)的治疗活性、保护活性和钝化活性分别为63.6%,85.7%和93.1%,与对照药宁南霉素(65.9%,86.4%和97.8%)相当;在50μg·m L-1浓度下,部分化合物表现出一定的抑菌活性,其中1,3-二甲基-5-氯-4-(2-噻吩)-腙基羰基吡唑(9b)与1-甲基3-三氟甲基-5-氯-4-(2-噻吩)-腙基羰基吡唑(9e)对小麦赤霉病菌(Gibberella zeae)的抑制率分别为42.5%和46.8%。

1,3-Disubstituted 5-chloro-4-pyrazole formyl hydrazines（7a, 7d, 7g and 7j） were prepared by ring-closing, chlorine acylation, oxidation, esterification and substitution addition reaction, using substituted hydrazine and substituted ethyl acetoacetate as starting materials. Twelve novel pyrazole acylhydrazone compounds（9a-91） were synthesized by addition reaction of 7 with furan or thiophene, respectively. The structures were characterized by 1n NMR, 13C NMR, IR and elemental analysis. The bioassay results showed that some title compounds showed certain antiviral activity against tobacco mosaic virus （TMV） at a concentration of 500 μg·mL^-1. Particularly, the protection, treatment and passivation activities of 1-phenyl-3-trifluoromethyl-5-chloro-4-（2-thiophene）-hydrazone carbonyl pyrazole （9k） were 63.6% , 85.7% and 93.1%, respectively, slightly lower than the contrast agents Ning- nanmycin （65.9%, 86.4% and 97.8% ）. Part of the compounds showed certain antibacterial activities against G. zeae, inhibition ratio of 1,3-dimethy-5-chloro4- （2-thiophene）-hydrazone carbonyl pyrazole （9b） and 1 -methy-3-trifluoromethyl-5 -chloro-4- （ 2-thiophene ） -hydrazone carbonyl pyrazole （ 9e ） were 42.5% and 46.8% at 50 trg · mL-I, respectively.