分别将6种脂肪酸与二氨基硫脲反应,合成了6种含不同碳数的3-脂肪基-1,2,4-三唑(1a～1f),其中化合物1e和1f为首次合成.在三氯氧磷存在下,分别将化合物1a～1f与4-吡啶甲酸和2,6-吡啶二甲酸反应,首次高产率合成了12种三唑并噻二唑衍生物(2a～2f)和(3a～ 3f).为对比引入3-脂肪基和吡啶组块对生物活性的影响,分别合成了3-苯基含吡啶组块产物(5)、双枝3-苯基含吡啶组块化合物(6)、不含吡啶组块的化合物(7a～7c)和(8a ～8c).应用IR、1H NMR和HRMS等技术手段对19种新物质进行了结构表征,并研究了其对Cdc25B和PTP1B的抑制性能,研究结果表明,含有吡啶组块的双枝脂肪基化合物3b、3d、3e和3f对Cdc25B有良好的抑制活性,IC50值(mg/L)分别为1.12 ±0.27、2.72±1.07、0.72±0.05和4.97 ±0.93;化合物2b、3d和5对PTP1B表现出较高的抑制活性,IC50值(mg/L)分别为0.98 ±0.13、1.33 ±0.11和2.18±0.20.
参考文献
| [1] | 郑玉国;魏学;郭晴晴.双三唑希弗碱哒嗪酮衍生物的合成及其生物活性[J].应用化学,201128(09):1028-1034. |
| [2] | 柴安;薛思佳;卞王东.1,3,4-均三唑并[2,1-b]-1,3,4-噻二唑衍生物的合成及生物活性[J].有机化学,2008(07):1199-1203. |
| [3] | Holla B S;Sarojini B K;Akberali P M.Synthesis and Studies on Some New Nluorine Containing Triazolothiadiazines as Possible Antibacterial,Antifungal and Anticancer Agents[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,200641(05):657-663. |
| [4] | 赵卫光;王建国;袁德凯.吡啶类农药研究趋势及新发现的含吡啶环的天然活性物质[J].农药,200241(07):8-11. |
| [5] | 胡国强;谢松强;许秋菊.3-(5-取代苯基-[1,3,4]噁二唑-2-亚甲硫基)-5-吡啶-3-基-[1,2,4]三唑-4-胺的合成及抗菌活性[J].药学学报,200540(04):337-339. |
| [6] | Park H;Bahn Y J;Jung S K.Discovery of Novel Cdc25 Phosphatase Inhibitors with Micromolar Activity Based on the StructureBased Virtual Screening[J].Journal of Medicinal Chemistry,200851(18):5533-5541. |
| [7] | He Y T;Xu J;Yu Z H.Discovery and Evaluation of Novel Inhibitors of Mycobacterium Protein Tyrosine Phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic Acid Scaffold[J].Journal of Medicinal Chemistry,201356(03):832-842. |
| [8] | Shiradkar M;Kumar G V S;Dasari V.Clubbed Triazoles:A Novel Approach to Antituber Cular Drugs[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,200742(06):807-816. |
| [9] | Karthikeyan M S;Holla B S;Kumari N S.Synthesis and Antimicrobial Studies of Novel Dichlorofluorophenyl Containing Minotriazolothiadiazines[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,200843(02):309-314. |
| [10] | Anetta Dzygiel;Elzbieta Masiukiewicz;Barbara Rzeszotarska.Acetylation of 5-Amino-1 H-[1,2,4]triazole Revisited[J].Journal of Agricultural and Food Chemistry,200250(06):1383-1388. |
| [11] | Michael J S;David R C;Rachel Reynolds.Efficient and Regiospecific One-Pot Synthesis of Substituted 1,2,4-Triazoles[J].Organic Letters,20046(17):2969-2971. |
| [12] | Shiradkar M R;Murahari K K;Gangadasu H R.Synthesis of New S-deriv Atives of Clubbed Triazolyl Thiazole as Anti-Mycobacteriurn Tuberculosis Agents[J].Bioorganic and Medicinal Chemistry Letters,200715(12):3997-4008. |
| [13] | Greg Buhrman;Benjamin Parker;Jungsan Sohn.Structural Mechanism of Oxidative Regulation of the Phosphatase Cdc25B via an Intramolecular Disulfide Bond[J].Biochemistry,200544(14):5307-5316. |
| [14] | Sumio Shimizu;Masaru Ogata.Novel Route to 1-Vinyl-1,2,4-triazoles by the Fluoride-catalyzed Peterson Reaction of 1-[Bis(trimethylsilyl) methyl]-1,2,4-triazole with Carbonyl Compounds[J].Journal of Organic Chemistry,198752(11):2314-2315. |
| [15] | Moulin A;Mathieu B;Blayo A L.Synthesis of 3,4,5-Trisubstituted-1,2,4-Triazol-es[J].CHEMICAL REVIEWS,2010110(04):1809-1827. |
| [16] | Elwahy A H M;Masaret G S.Synthesis of Novel Benzo-Substituted Macrocyclic Schiff Bases Containing Two Triazole Rings[J].Journal of Heterocyclic Chemistry,200744(06):1475-1484. |
| [17] | Juan J.Manclús;María J.Moreno;Emma Plana.Development of Monoclonal Immunoassays for the Determination of Triazole Fungicides in Fruit Juices[J].Journal of Agricultural and Food Chemistry,200856(19):8793-8800. |
| [18] | Ned D Heindel;Jack R Reid.7H-[1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones by Deamination Cyclization of S-Acrylates of 4-Amino-3 (3 H)-1,2,4-triazolethiones[J].Journal of Organic Chemistry,198045(12):24792482. |
| [19] | Dengjiang LI;Deqinglong;Heqing FU.Synthesis of 1,4-Bis[(3-Aryl)-s-Triazolo (3,4-b)-(1,3,4) Thiadiazole-6-yl]Benzenes[J].Synthetic Communications,200535(19):2495-2500. |
| [20] | Huang W G;Jiang Y Y;Li Q.Synthesis and Biological Evaluation of (±)-Cryptotanshinone and Its Simplified Analogues as Potent CDC25 Inhibitors[J].Tetrahedron,200561(07):1863-1870. |
| [21] | Sun L P;Shen Q;Piao H H.Synthesis and Biological Evaluation of (±)-3-(2-(2-Fluorobenzyloxy) Naphthalen-6-yl)-2-aminopropanoic Acid Derivatives as Novel PTP1B Inhibitors[J].EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,201146(09):3630-3638. |
| [22] | He X P;Li C;Jin X Q.Microwave-assisted Construction of Triazole-linked Amino Acid-glucosideconjugates as Novel PTP1B Inhibitors[J].New Journal of Chemistry,201135(03):622-631. |
上一张
下一张
上一张
下一张
计量
- 下载量()
- 访问量()
文章评分
- 您的评分：
-
10%
-
20%
-
30%
-
40%
-
50%