哒嗪酮衍生物的合成和生物活性研究

合成了16个含哒嗪酮环新化合物, 所有化合物结构均通过¹H NMR, IR和元素分析确证. 生物活性初步研究结果表明, 在200 mg/kg浓度下, 化合物7a, 7b, 7c和7d对二龄家蝇幼虫具有较好的杀虫活性, 对三龄蝗蝻活性不明显.     

有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成

氨基甲酸酯衍生物;有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成     

双三唑席夫碱哒嗪酮衍生物的合成及其生物活性

设计合成了9种未见文献报道的双三唑席夫碱哒嗪酮化合物。用1H NMR、13C NMR、IR及元素分析表征结构。生物活性初步结果表明,在500 mg/L浓度下部分化合物对黄瓜花叶病毒(CMV)、小麦赤霉病菌(G.zeae)、辣椒枯萎病菌(F.oxysporum)和苹果腐烂病菌(C.mandshurica)有一定抑制作用。     

新型1,3,4-噻二唑硫醚哒嗪酮衍生物的合成及生物活性

以糠氯酸为原料,与叔丁基肼盐酸盐环合制得2-叔丁基-4,5-二氯-3(2H)哒嗪酮,随后与新合成的5-胺基-1,3,4-噻二唑-2-硫醇衍生物发生亲核取代反应,反应合成了11个新型1,3,4-噻二唑硫醚哒嗪酮衍生物（7a~7k）。化合物的结构均经¹H NMR、¹³C NMR、IR、ESI-MS和元素分析表征。采用生长速率法测试了化合物对小麦赤霉病菌(G. zeae)、辣椒枯萎病菌(F. oxysporum)、苹果腐烂病菌(C. mandshurica)3种菌株的杀菌活性,在100 mg/L浓度下,化合物7a对小麦赤霉病菌的抑制率38.6%;7f对辣椒枯萎病菌的抑制率为54.6%。      

哒嗪酮苷类化合物的合成研究

一些嘧啶系列的苷具有较强的生理活性,其中5-氟脲苷是有效的抗癌药物。而哒嗪与嘧啶具有同分异构关系,那么,哒嗪苷类化合物是否也有相似的生理活性呢?六十年代初,Wagner等开展了这一领域的研究;到七十年代中期,Katz等合成了与天然     

5-芳甲氧基-3(2H)-哒嗪酮衍生物的设计、合成与生物活性

为寻找新型昆虫生长调节活性化合物, 设计合成了15个未见文献报道的5-芳甲氧基取代的3(2H)-哒嗪酮衍生物, 所有化合物结构均通过¹H NMR, IR和元素分析确证. 初步生物活性研究表明, 化合物8o对2龄家蝇幼虫有明显的抑制作用; 化合物8a, 8c, 8g和8j对3龄蝗蝻显示出较好的生物活性. 对目标化合物的构效关系亦进行了初步探讨.     

含三元杂环席夫碱类衍生物的合成及生物活性研究

设计合成了10个新型的含三元杂环席夫碱类衍生物,所有化合物结构通过1H NMR,13C NMR,IR和元素分析确证,生物活性初步研究结果表明,在50 mg/L浓度下,目标化合物对小麦赤霉菌(G.zeae)、苹果腐烂病菌(C.mand-shurica)和辣椒枯萎病菌(F.oxysporum)具有一定的抑制活性.     

哒嗪酮类α1-肾上腺素受体拮抗剂的合成和生物活性研究

将苯(氧)乙胺和苯氧烷胺类α1-肾上腺素受体拮抗剂中的苯(氧)乙胺、苯氧烷胺片段引入哒嗪酮类化合物中,设计、合成了30个新的含哒嗪酮环的α1-肾上腺素受体拮抗剂．所有新化合物的结构均经1H NMR,IR,HRMS确证．生物活性测试表明28个目标物对α1-肾上腺素受体有较好的拮抗作用(pA2>6．00),化合物6o,6p,6q,6v,6x,6y,10c,10d的pA2值>7．00．     

丁苯酞-哒嗪酮衍生物的设计、合成及其抗凝活性研究

为了提高丁苯酞的抗血小板凝集活性,以6-氨基丁苯酞为起始原料,经重氮化/还原、环化、水解、脱氯、醚化和磺酰化反应合成了20个新型的丁苯酞-哒嗪酮衍生物,其结构经1H-NMR、13C-NMR和HRMS确证。体外抗血小板凝集活性测试结果表明:化合物6a、6b和6k对二磷酸腺苷(ADP)诱导的血小板凝集的抑制活性(IC50 = 44.9-180.0 μmol/L)优于先导化合物丁苯酞(IC50 = 1252 μmol/L)和阳性对照阿司匹林(IC50 = 1140 μmol/L);同时化合物 6b(IC50 = 63.6 μmol/L)和6k(IC50 = 191.9 μmol/L)对花生四烯酸(AA)诱导的血小板凝集也表现出显著的抑制活性。本研究为丁苯酞-哒嗪酮骨架在治疗缺血性脑卒中方面的研究提供了理论参考。     

六氢哒嗪衍生物的合成与生物活性研究

以六氢哒嗪为先导化合物, 合成了13个新型六氢哒嗪衍生物, 通过IR, 1H NMR和MS进行了结构表征, 对其中3个代表性的化合物培养了单晶, 获得了X射线衍射结构. 初步的生测结果表明部分化合物具有除草活性.     

Microwaves in organic synthesis: Facile synthesis of biologically active pyridazinone and iminopyridazine derivatives

Condensation of Wittig reagents 1a,b with arylhydrazones 2a,b by conventional and by microwave heating techniques furnished the corresponding pyridazines 3a‐e . The arylhydrazones 7a,b were allowed to react with 1a,b under the same conditions to produce the pyridazinones 10a,b and iminopyridazines 11a,b respectively. On the other hand, the arylhydrazones 12a‐c reacted with 1a to afford the pyridazinones 13a‐c . Treatment of 3b with dimethylformamide dimethyl acetal (DMFDMA) produced the adduct 15 . The utility of microwave heating technique led to the reduction of the reaction times to few minutes and to the improvement of the yields of the products. The in vitro biological activity of some newly prepared compounds against four types of fungi was studied.     

Design,synthesis, and bioactivities of novel pyridazinone derivatives containing 2-phenylthiazole or oxazole skeletons

A series of novel pyridazinone derivatives were designed and synthesized by replacing 4-(tert-butyl)phenyl moiety of pyridaben with 2-phenylthiazole or oxazole fragments via activity substructure connecting approach. The structures of all target compounds were characterized through NMR, MS, and elemental analysis. Bioassay results exhibit that most compounds showed potent bioactivities against Aphis fabae, Tetranychus urticae, Erysiphe graminis, and/or Puccinia polysora. Among the newly synthesized compounds, 2-(tert-butyl)-4-chloro-5-(((2-phenylthiazol-4-yl)methyl)thio)pyridazin-3(2H)-one ( 12b ) displays remarkable insecticidal activity against A fabae. Its LC₅₀ value (2.73 mg/L) is better than that of pyridaben (5.46 mg/L), although inferior to that of imidacloprid (0.51 mg/L). In addition to its extraordinary insecticidal activity, compound 12b also exerts 96.9% fungicidal activities against P polysora at 500 mg/L in vivo, significantly superior to that of pyridaben (50.0%), while slightly lower than that of tebuconazole (100%). This article discusses the synthesis, bioassay results, and structure-activity relationship of this series of novel pyridazinone derivatives.     

Study of the synthesis,antiviral bioactivity and interaction mechanisms of novel chalcone derivatives that contain the 1,1-dichloropropene moiety

A series of novel chalcone derivatives that contain the 1,1-dichloropropene moiety was designed and synthesized. Bioactivity assays showed that most of the target compounds exhibited moderate to good antiviral activity against tobacco mosaic virus (TMV) at 500 μg/mL. Among the target compounds, compound 7h showed the highest in vivo inactivation activity against TMV with the EC₅₀ and EC₉₀ value of 45.6 and 327.5 μg/mL, respectively, which was similar to that of Ningnanmycin (46.9 and 329.4 μg/mL) and superior to that of Ribavirin (145.1 and 793.1 μg/mL). Meanwhile, the microscale thermophoresis and fluorescence spectroscopy experiments showed that the compound 7h had a strong interaction with the tobacco mosaic virus coat protein.     

多氟苯脲衍生物的合成研究

以三氟苯胺、对取代苯胺和固体光气为原料,基于异氰酸酯法合成了两种多氟苯脲衍生物。产品结构经IR,1H NMR,ESI-MS和元素分析表征,并对反应条件和波谱性质进行了讨论。     

Study on the bioactivity changes of hydroxylated sulfonylureas derivatives: A possible metabolism

Some new sulfonylureas and their hydroxylation products had been synthesized from 2-amino-4-methylpyrimidine. Their bioactivities against E. coli AHAS II in vitro were tested and the results indicated that the hydroxylation decreased the inhibition activities of sulfonylureas significantly. Subsequently herbicidal tests against stem-growth of barnyard grass and root-growth of rape confirmed the above conclusion. The preliminary molecular docking studies were also carried out to investigate the binding modes of non-hydroxylated and hydroxylated sulfonylureas with AHAS.     

四苯基卟啉及其衍生物的合成

对四苯基卟啉及其衍生物的合成进行了大量研究，探讨了近三十种常用的有机溶剂中，选用三十五种常用的有机酸、无机酸催化吡咯和苯甲醛缩合。结果发现：吡咯与相应的取代苯甲醛在回流状态下缩合得到目标化合物。     

Synthesis and bioactivity of beta-carboline derivatives

The beta-carboline alkaloids possess a wide diversity of important biochemical effects and pharmacological properties. A series of beta-carboline derivatives were synthesized from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 by a sequential one-pot synthesis method. In vitro anti-bacterial, insecticidal, and cytotoxic activities of all synthesized compounds were investigated by the tablet diffusion, leaf disc, and MTT methods, respectively. Some of the compounds (1-1, 1-2, 1-3 and 1-12) exhibited obvious anti-bacterial effects and some (1-3) had significant cytotoxic activities against tumor cells 3LL, MCF-7, BGC-823 and QGY-7701, with IC50 values of 7.79, 5.75, 3.53 and 4.02 microg/mL, respectively. No insecticidal activity against third stage instar larvae of Mythimna separata Walker were observed under the tested concentration.     

A mild and efficient synthesis of a chiral pyridazinone derivative

We found a mild and efficient reaction condition for construction of a chiral 5-methyl-4,5-dihydropyridazin-3(2H)-one from a chiral β-methyl γ-ketocarboxylic acid via the corresponding acid hydrazide without racemization. Furthermore, we demonstrated that this two-step reaction can be attained by one-pot reaction. This method could be applied to various kinds of substrates because of the mild reaction conditions.     

Study on the synthesis and cytotoxicity of new quinophenoxazine derivatives

We have synthesized several new quinophenoxazine analogues and tested their cytotoxicity activities. The results showed that the compounds, 4a and 4b, possessing phenyl ring in the structure have almost same pharmacological capacity with A-62176. This finding suggests that the phenyl ring portion is important to this series of compounds for the activity expression.