Synthesis of benzazoles, 1,3,4-oxadiazoles,and 1,3,4-thiadiazoles containingβ-alkylthioethyl radicals

By the condensation of hydrochlorides of iminoesters of-alkylthiopropionic acids with o phenylenediamine, o-aminophenols, hydrazides of acids, and thiosemicarbazide, we have synthesized 2-substituted benzimidazoles and benzoxazoles, 2, 5-disubstituted 1, 3, 4-oxadiazoles, and 2-amino-5-substituted 1, 3, 4-thiadiazoles containing-alkylthiioethyl fragments.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 115–118, January, 1994.     

含1,3,4-噁二唑和1,3,4-噻二唑的硫醚类化合物的合成

在KOH作用下,芳甲酰肼1a～1e与CS2环化生成5-芳基-2-巯基-1,3,4-噁二唑(2a～2e);将2a～2e与氯乙酸乙酯反应,生成2-(5-芳基-1,3,4-噁二唑)硫基乙酸乙酯(3a～3e);3a～3e肼解得2-(5-苯基-1,3,4-噁二唑-2-硫基)乙酰肼(4a～4e);4a～4e与芳酰基异硫氰酸酯5a～5d反应得到双酰基氨基硫脲衍生物A1～A19;A1～A19在H2SO4催化下环合得到目标化合物B1～B19;目标化合物的结构经IR,1H NMR,MS,HRMS确证.     

新型1,3,4-噻二唑衍生物的合成

以5-氨基-2-巯基-1,3,4-噻二唑为起始原料,对其2-位的巯基、5-位的氨基及杂环上3-位N原子进行结构修饰,合成了24个新型的1,3,4-噻二唑衍生物,其结构经1H NMR,13C NMR,IR和元素分析表征。     

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)]和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c)],对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼,随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.     

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

以5-对甲苯基-1-氨基-2-巯基-1,3,4-均三唑和取代苯氧乙酰异硫氰酸酯为原料, 合成了10个未见文献报道的5-对甲苯基-2-取代苯氧乙酰氨基均三唑并[2,1-b]-1,3,4-噻二唑类化合物, 通过元素分析, 1H NMR, IR和MS确定化合物的结构, 初步生物活性测试表明目标化合物具有较好的除草活性.     

Copper-catalyzed direct cross coupling of 1,3,4-oxadiazoles with trans-β-halostyrenes: synthesis of 2-E-vinyl 1,3,4-oxadiazoles

The first direct C–H alkenylation of 1,3,4-oxadiazoles with trans-β-halo olefinic system has been carried out using a combination of CuI/DMEDA as a catalyst. A wide range of 2-E-vinyl-substituted oxadiazoles were obtained in high yields (85–93%).     

含氟1,3,4-噁唑啉和1,3,4-噁二唑类化合物的合成及其抗癌活性

对氟苯甲酰腙与乙酸酐或丙酸酐反应后再脱水环化制得2-苯基-3-乙酰基-5-对氟苯基-1,3,4-噁唑啉(3)或2-苯基-3-丙酰基-5-对氟苯基-1,3,4-噁唑啉(4).N-对氟苯甲酰基-N′-苯甲酰肼在POCl3存在下脱水环化制得2-苯基-5-对氟苯基-1,3,4-噁二唑(6).新化合物3,4和6的结构经1H NMR,IR,MS和元素分析表征.用MTT方法评价了其对HepG-2,A549-1和231-2癌细胞株的体外生长抑制活性.结果表明,3,4和6均具有潜在的体外抑制癌细胞生长活性,其中3的活性最强.     

1,3,4-噻二唑衍生物合成及其生物活性研究进展

1,3,4-噻二唑是含有N、S杂原子的五元杂环化合物,具有多种生物活性。目前,1,3,4-噻二唑及其衍生物广泛用于生物、医药等领域,尤其在抗菌、抗肿瘤、抗癌等方面的研究已取得重大突破。由于1,3,4-噻二唑结构的特殊性以及优越的生物活性,对其进行研究有重要意义。本文主要概述了近年来1,3,4-噻二唑衍生物的几种合成方法以及其在抗菌、抗肿瘤、抗癌方面的研究进展。     

[4 + 1] Cyclization of benzohydrazide and ClCF2COONa towards 1,3,4-oxadiazoles and 1,3,4-oxadiazoles-d5

A facile synthesis of 1,3,4-oxadiazoles and 1,3,4-oxadiazoles-d₅ via [4 + 1] cyclization of ClCF₂COONa with non-amine compounds containing amino groups is developed. Of note, this is the first time that halofluorinated compounds are used as C1 synthon to construct deuterated nitrogen-heterocyclic compounds. The current protocol features simple operation, readily accessible raw materials, wide substrate scope and valuable products     

Cyclocondensation of 2-Amino-1,3,4-thiadiazoles with β-Sulfonylvinyltrifluoromethyldiols

A series of CF₃-containing 6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ols was obtained by the interaction of 2-amino-1,3,4-thiadiazoles with -sulfonylvinyltrifluoromethyldiols and their stereochemistry was established. The structure of 5-(phenylsulfonyl)-7-(trifluoromethyl)-6,7-dihydro-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-ol was confirmed by X-ray crystallography.     

One-pot synthesis of 2,5-disubstituted-1,3,4-thiadiazoles under ultrasonic irradiation

A facile one-pot synthesis of 2,5-disubstituted-1,3,4-thiadiazoles was achieved by ultrasonic irradiation of a mixture of 1- naphthylacetyl chloride,NH_4CNS,CH_2Cl_2 and PEG-400 for 1.5 h at 10-20℃and subsequent irradiation for 1.5h in the presence of N-arylglycine hydrazides.This method requires short time and gives thiadiazoles in high yields.     

Reactions of α-mercaptocarboxylic acid hydrazides with triethyl orthoesters: synthesis of 1,3,4-thiadiazin-5(6H)-ones and 1,3,4-oxadiazoles

Reactions of α-mercapto-β-phenylpropionic and α-mercaptophenylacetic acid hydrazides with triethyl orthoesters were conducted under N₂ in glacial acetic acid and resulted in the formation of two groups of products, derivatives of 1,3,4-thiadiazin-5(6H)-ones and 2-(1-mercaptomethyl)-1,3,4-oxadiazoles. When conducting the same transformations on α-mercaptophenylacetic acid hydrazide in the presence of air, two different products from the 1,3,4-oxadiazole family, the appropriate bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides and 2-benzyl-1,3,4-oxadiazoles, were formed with the liberation of free sulfur. The oxygenated bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides were reduced to the corresponding 2-(1-mercaptomethyl)-1,3,4-oxadiazoles with the use of zinc powder under mild conditions.     

新型1,3,4-噻二唑衍生物的合成及抗肿瘤活性

以取代的苯乙酸为起始原料,通过成环、偶联、脱保护基并引入苯磺酰胺等反应得到了系列2,5-二取代-1,3,4-噻二唑类化合物,并利用1H NMR,13C NMR和HRMS对目标化合物进行了结构表征.用四甲基偶氮唑盐(MTT)法测试了目标化合物体外抑制前列腺癌细胞(PC-3)、乳腺癌细胞株(MDA-MB-231)和白血病细胞(K562)等肿瘤细胞的增殖活性.结果显示,部分目标化合物具有较好的抗肿瘤细胞增殖活性,其中(S)-N-(5-([1,1'-联苯]-4-基甲基)-1,3,4-噻二唑-2-基)-2-氨基-3-(4-溴苯基)丙酰胺(6a)和(S)-N-(5-([1,1'-联苯]-4-基甲基)-1,3,4-噻二唑-2-基)-2-氨基-3-苯基丙酰胺(6b)对K562细胞的活性与阳性对照药棉酚相当.     

手性1,3,4-噁二唑硫醚衍生物的合成

以5-取代-2-巯基-1,3,4-噁二唑为亲核试剂,与手性5-烷氧基-3,4-二溴-2(5H)-呋喃酮发生Michael反应,合成了6种新的手性1,3,4-噁二唑硫醚衍生物(产率55%～67%),其结构经1H NMR, 13C NMR, IR和HR-MS确证.     

色酮连1,3,4-三唑硫醚类化合物的合成

色酮类化合物广泛存在于天然产物中,因其良好的生理活性而一直受到关注.许多杂环取代色酮化合物也具有优良的抗癌、抗菌、降血脂、降血糖、促进代谢和防止心率不齐等生理活性[1,2].1,3,4-三唑类化合物不但有广谱的抗病毒、调节植物生长等生物活性,它同时又是一种重要的有机合成中间体.近年来的研究表明,将1,3,4-三唑引入某些活性分子能明显改善其活性[3].     

2,5—二芳基取代—1,3,4三唑的合成

２，５－二芳基取代－１，３，４－三唑的合成花文廷徐东成程铭（北京大学化学系１００８７１）１，３，４－三唑类化合物大多具有良好的杀虫和抗真菌等药效［１～３］。近年还发现，某些２，５－二取代芳基三唑有显著的中止妊娠的作用［４，５］，对老鼠的实验表明，其避...     

一种水溶性1,3,4-噻二唑类化合物的合成及生物活性

噻二唑与芳香醛反应制得一系列苯腙化合物,该类化合物再与氯乙酰氯反应得到关键中间体3,中间体3与三乙胺反应最终得到水溶性目标产物,对所有目标产物进行了红外、核磁氢谱、质谱和元素分析表征。水溶性实验证明,该类化合物在25℃的水中均具有大于10g的溶解度。并且生物活性实验表明,该类化合物对枯草杆菌(B.subtilis),大肠杆菌(E.coli),普通变形杆菌(P.vulgaris)和金黄色葡萄球菌(S.aureus)都具有明显的抑菌活性。     

1,3,4-噻二唑基芳酰基脲的合成和生物活性

以2-氨基-5-取代苯基-1,3,4噻二唑和2,6-二氟苯甲酰异氰酸酯为起始原料,合成了10个未见文献报道的含1,3,4-噻二唑环的芳酰基脲类衍生物。通过1H NMR,IR,ESI-MS和元素分析确定化合物的结构。初步生物活性测试表明,此类化合物具有一定的杀虫活性,其中化合物3d (3,5-(CH3)2)和3g (4-C4H9)对蚕豆蚜的杀虫死亡率达到90%以上.     

Synthesis of ribonucleoside analogues containing thio-substituted 1,3,4-triazole as heterocyclic base

New ribonucleoside analogues containing thio-substituted 1,3,4-triazole as heterocyclic base have been synthesized via condensation of the central intermediate 1 with various acids,esters,amides,and anhydrides in anhydrous solvent followed by deprotection.     

Study on the Three-dimensional Quantitative Structure-activity Relationship of Pyridazinonyl-substituted 1,3,4-Thiadiazoles

The three-dimensional quantitative structure-activity relationships of a series of 5-[ 1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl]-2-arylamino-1,3,4-thiadiazoles, related to the fungicidal activity, were studied using the comparative molecular field analysis （CoMFA）. The results show that the contributions of steric and electrostatic fields to the activity are 0.505 and 0.495, respectively. The cross-validated q^2 and the correlation coefficient r^2 for the model established by the study are 0.769 and 0.938, respectively, with the F value of 60.996, and the standard deviation s of 0.074. These values indicate that the model is significant and has good predictability. The analysis results are in good agreement well with the study of 2D-QSAR, and offered important structural insights into designing highly active compounds prior to synthesis.