新型噻唑并[3,2-a]嘧啶衍生物的合成及其抗肿瘤活性

以取代苯肼盐酸盐为原料,通过Vilsmeier-Haack,Biginelli和Knoevenagel等多步反应合成了9个含有吡唑取代基的噻唑并[3,2-a]嘧啶衍生物,并利用IR,1H NMR,13C NMR,ESI-MS和HRMS对目标化合物进行了结构表征.用四甲基偶氮唑盐(MTT)法测试了目标产物对人前列腺癌PC-3细胞和人肝癌Hep G2细胞的体外抗增殖活性,部分化合物表现出了较好的生物活性,其中化合物5b,5c,5g和5i对PC-3细胞的抗肿瘤活性优于阳性对照药5-氟尿嘧啶,IC50值分别为29.98,27.69,26.36和12.56μmol/L.进一步的研究表明,化合物5i能够诱导PC-3细胞凋亡,并使其周期阻滞在G2/M期.     

5-(4-氟苯基)-N-1-(3-羟基金刚烷基)-7-三氟甲基吡唑并[1,5-a]嘧啶-3-酰胺的合成及其抗肿瘤活性

以乙氧基甲叉基氰乙酸乙酯和对氟苯乙酮为起始原料,设计并合成了新化合物5-(4-氟苯基)-N-1-(3-羟基金刚烷基)-7-三氟甲基吡唑并[1,5-a]嘧啶-3-酰胺(7),其结构经~1H NMR,IR和HR-MS(ESI)表征。采用MTT法测定了其对人乳腺癌细胞(Bcap-37)、人宫颈癌细胞(He La229)、人肝癌细胞(QGY-7701)和人肺癌细胞(A549)体外抗肿瘤细胞的增殖活性。结果表明:7对受试细胞的抑制活性较好,其IC_(50)值分别为23.9μmol·L~(-1),29.8μmol·L~(-1),31.4μmol·L~(-1)和21.7μmol·L~(-1)。     

2-苄硫基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰腙类衍生物的合成及其抑菌活性

采用活性单元拼接法在1,2,4-三唑并[1,5-a]嘧啶环的2-位和7-位分别引入苄基硫醚和不同的酰腙单元,设计并合成了12个新型2-苄硫基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰腙类衍生物(1a～1l),其结构经1H NMR,IR,MS和元素分析表征。初步生物活性测试结果表明,1a～1l对黄瓜灰霉菌具有明显的抑制活性。     

2-苄砜基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰腙类衍生物的合成及抑菌活性研究

以2-苄硫基-5-甲基-7-羟基-1,2,4-三唑并[1,5-a]嘧啶为起始原料,设计合成了24个新型的2-苄砜基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰腙类化合物5a～5x,通过1H NMR,IR,MS和元素分析对目标化合物进行了结构表征.初步生物活性测试结果表明,在50μg/mL浓度下,N-[2-苄砜基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰基]-4-甲氧基苯甲醛腙(5k),N-[2-苄砜基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰基]-2-氯-5-硝基苯甲醛腙(5p)和N-[2-苄砜基-5-甲基-1,2,4-三唑并[1,5-a]嘧啶-7-氧乙酰基]-苯丙烯醛腙(5s)对黄瓜灰霉病菌的抑制率均超过70%.     

微波辐射下合成2-甲硫基-3-氰基-7-取代苯基吡唑并[1,5-a]嘧啶及生物活性的研究

利用取代烯胺酮1与3-甲硫基-4-氰基-5-氨基-1H-吡唑(2)反应,用传统和微波2种方法合成了6种化合物2-甲硫基-3-氰基-7-取代苯基吡唑并[1,5-a]嘧啶(3a～3f),化合物的结构均经元素分析,IR,1H NMR所证实.对比两种方法,微波辐射具有用时少、环境友好、易纯化和产率高的特点,同时,探讨了反应可能的机理,并对所有化合物的杀菌和除草活性进行了测试.     

5H-噻唑并[3,2-a]嘧啶类化合物的合成及抗肿瘤活性研究

以芳醛、硫脲等为起始原料,通过Biginelli反应合成二氢嘧啶类化合物,再与取代的溴代苯乙酮发生Hantzsch环合反应得到目标化合物。所有化合物的结构都经过1H NMR、13C NMR、IR和HRMS表征确认。在此基础上以MCF-7、A549和HT-29为靶细胞,顺铂为阳性对照物,采用噻唑蓝检测法进行初步体外抗肿瘤活性筛选。结果表明,化合物3c对HT-29的体外抗肿瘤活性与对照药物相当,值得进一步研究。     

3-芳基-6-甲酰胺吡唑并[1,5-a]嘧啶类化合物的 合成及其抗癌活性研究

以乙酰乙酸乙酯和N,N-二甲基甲酰胺二甲缩醛为原料,通过缩合、环合、水解和酰胺化4步反应合成了一系列新的2,7-二甲基-3-芳基-6-甲酰胺吡唑并[1,5-a]嘧啶类化合物（6a~6f）,其结构经¹H NMR、 ¹³C NMR、 IR、 MS和元素分析。采用MTT法,以索拉菲尼(sorafenib)为阳性对照药,测定了化合物对人肝癌细胞株(HepG2)的体外抗增殖活性。结果表明：6a~6f具有一定的抗癌活性,其中化合物6a对人肝癌细胞株(HepG2)的抗增殖活性(IC₅₀=10.2 μmol·L^-1)和阳性对照药索拉菲尼(IC₅₀ = 7.9μmol·L^-1)相当。     

1-异丙基-3-异丙烯基-1H-吡唑并[3,4-d]嘧啶-4-胺的合成、表征及抗肿瘤活性

以3-碘-1H-吡唑并[3,4-d]嘧啶-4-胺(2)为原料,经过N-烷基化、Suzuki偶联反应得到目标化合物1-异丙基-3-(异丙烯基)-1H-吡唑并[3,4-d]嘧啶-4-胺(1),两步反应总收率57.0 %。产物及中间体结构经₁^H NMR、_1³C NMR、ESI-MS以及X-射线单晶衍射进行表征。并对该Suzuki反应条件进行研究,确定最佳条件为：Pd(dppf)Cl₂的用量为n (Pd(dppf)Cl₂) : n (化合物3) = 0.06 : 1;物料比为n(异丙烯基硼酸): n(化合物3)= 1.6 : 1;反应溶剂为N,N-二甲基甲酰胺;反应温度为100 ℃;反应时间2 h,在最佳反应条件下,该Suzuki偶联反应收率达到68.2 %。体外抗肿瘤活性测试表明,产物(1)对MCF-7、A549、PC-3、HepG2和SGC-7901增殖均有明显的抑制活性,特别抑制MCF-7的IC₅₀值达到10.6 μmol?L_-1^。     

新型三环系稠杂环[1,2,4]-三唑并[1,5-a][1]-苯并氮杂(艹卓)及[1,2,4]-三唑并[1,5-a]-喹啉的合成

α-四氢萘酮的乙氧羰基腙(1)经LTA氧化, 得到α-偶氮-α-乙酰氧基化合物2. 在AlCl3作用下, 化合物2脱去乙酰氧基产生重氮正离子中间体3, 再经与腈的1,3-偶极环加成、 [1,2]-迁移扩环、碱性水解和与苦味酸作用, 得到新型[1,2,4]-三唑并[1,5-a][1]苯并氮杂(艹卓)苦味酸盐6a～6c. 以2,3-二氢-1-茚酮为底物, 采用相同的合成路线, 合成了1,2,4-三唑并[1,5-a]-二氢喹啉苦味酸盐12a～12c.     

Synthesis and Antiproliferative Activity of Novel [1,2,4]Triazolo[1,5-a]pyrimidine-7-amine Derivatives

A series of novel N-anilino-2-substituted-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-7-amine derivatives was prepared and evaluated for their in vitro antiproliferative activity against two cancer cell lines,Bel-7402 and HT-1080.Most of the compounds inhibited the cell proliferation at a low concentration.Seven compounds,VI5,VI7,VI10,and VI12―VI15,possessed marked antiproliferative activity superior to that of cisplatin.Of these seven initial hits,compound VI10 was the most active.     

Design, Synthesis, and Hypnotic Activity of Pyrazolo [1,5-a]pyrimidine Derivatives

On the basis of the Zaleplon structure, novel pyrazolo[1,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate. The structures of the derived target compounds were confirmed by their IR and ^1H-NMR spectroscopic data. The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, whilc derivative 1c was the most potent one.     

Facile Syntheses of New Pyrazolo[1,5-a] pyrimidines Derivatives via Reactions of Enaminones with Aminopyrazole

Ethyl 7-aryl-2-benzyhhiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates （3a-3f） were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzyhhio4-ethoxycarbonyl-1 H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurmehts, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.     

Copper(I)-Catalyzed Tandem Cyclization/Condensation Reaction to Novel 4,5-Dihydropyrazolo[1,5-a]quinolines and Pyrazolo[1,5-a]indoles

A facile copper(I)-catalyzed tandem reaction for the synthesis of 4,5-dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles is reported here. High efficiency and good yields are displayed in this transformation under mild reaction conditions.      

Pyrazolo[1,5-a]pyrimidine-Dioxaborinine Hybrid Dyes: Synthesis and Substituent Effect in the Photophysical Properties

A novel family of pyrazolo[1,5-a]pyrimidine-dioxaborinine (PP-DB) hybrid dyes was synthesized by the direct construction of the dioxaborinine (DB) fragment on the pyrazolo[1,5-a]pyrimidine (PP) ring, which implies the formation of four new bonds in a one-pot manner. The dyes’ optical properties were investigated and compared with the starting pyrazolo[1,5-a]pyrimidines; a study evidencing large fluorescence quantum yields in products (φ_f up to 69 %) due to an intramolecular charge transfer (ICT) process from the PP core to a ring of DB (PP→DB) that is absent in precursors (φ_f=0.03–0.30). Time-dependent density functional theory (TD-DFT) calculations confirmed the fluorescence process involved in the novel dyes, where their ICT limits the non-radiative process due to the restricted rotation in the D−A system. The present work provides insight into how phenyl and DB ring incorporation impact the optical properties of this new group of hybrids dyes based on PP-DB.     

N-(1,2,4-三唑并[1,5-a]嘧啶-2-基)-N′-芳酰基硫脲的合成与生物活性

通过2-氨基-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶同芳酰基异硫氰酸酯反应, 合成了12种新的含杂环基的芳酰基硫脲, 用红外光谱、核磁共振氢谱和元素分析确证了其结构, 初步的生物活性测定试验表明部分目标化合物具有良好的生物活性, 尤其是对于双子叶植物表现出较高的除草活性.     

Cyanothioacetanilide Intermediates in Heterocyclic Synthesis,Part 1: Synthesis and Biological Evaluation of Some Novel Thiazole,Thiophene, Pyrazole,and Pyrazolo[1,5-a]Pyrimidine Derivatives

Some novel thiophenes (4a,b, 5, and 9a,b) were obtained from the cycloalkylation of the thiocarbamoyl group in the cyanothioacetanilide derivative (1) with α-halocarbonyl compounds. Also, the reaction of cyanothioacetanilide derivative with phenyl isothiocyanate in the presence of potassium hydroxide followed by in situ heterocyclization of the resulting adduct with α-halocarbonyl compounds furnished the corresponding thiazole (12, 14, and 15), pyrazole (19), and pyraozlo[1,5-a]pyrimidine (22, 25, and 26) derivatives. Compounds (4b, 5, 9a, 12, 13, 18, 22, 25, and 26) were tested to evaluate their antimicrobial activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Water-Mediated Selective Synthesis of Pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]Triazolo[1,5-a]quinazolin-5(4H)-one via Copper-Catalyzed Cascade Reactions

A convenient and sustainable synthesis of pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one through copper-catalyzed cascade reactions of 2-bromobenzoates with 1H-pyrazol-5-amines or 1H-1,2,4-triazol-5-amine under ligand-free conditions in water is presented. It is notable that aqueous medium turned out to be crucial for the chemoselective formation of the title compounds. Compared with literature protocols, this new method showed advantages such as simple and sustainable procedure, commercially available starting materials, and convenient reuse of the reaction medium together with the copper catalyst.     

新型2-甲基-5-羟基-7-氨基-吡唑[1,5-a]并嘧啶衍生物的合成

以3-甲基-5-氨基-吡唑和氰乙酸乙酯为原料,合成了2-甲基-5-羟基-7-氨基-吡唑[1,5-a]并嘧啶(2);2与芳胺的重氮盐溶液反应,合成了7个新型的2-甲基-5-羟基-6-芳基偶氮-7-亚氨基-吡唑[1,5-a]并嘧啶衍生物,收率87%~93%,其结构经~1H NMR,IR和ESI-MS表征。