新型吡唑酰腙类化合物的合成及其生物活性

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500 μg·mL^-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50 μg·mL^-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%。

Synthesis and Biological Activities of Novel Acylhydrazone Compounds Containing Pyrazole Group

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~9l) were synthesized by addition reaction of 7 with furan or thiophene, respectively. The structures were characterized by 1 H NMR, 13 C 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-chloro-4-(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 μg·mL-1 , respectively.