新型3-萘基-1,3-噻唑烷-4-酮衍生物的微波促进合成及其抗菌活性研究

利用微波促进的多组分一锅法, 在封管条件下, 以萘胺、芳醛和巯基乙酸为原料, 4-二甲氨基吡啶(DMAP)/N,N’-二环已基碳二亚胺(DCC)为催化剂, 合成了系列新的噻唑烷酮衍生物, 该反应具有时间短、操作简便等优点. 目标化合物通过IR, NMR, MS和元素分析等方法确定结构. 初步测试了化合物对丁香假单胞杆菌黄瓜角斑病菌致病变种、番茄灰霉病菌和黄瓜白粉病菌抑制活性, 结果表明: 部分化合物对黄瓜白粉病菌有显著抑制作用, 但对前两种植物病菌抑制效果不明显.     

3-芳基噻唑烷-4-酮-2-酰胺的合成及其抗肿瘤活性研究

合成了系列新的3-芳基噻唑烷-4-酮-2-酰胺衍生物,并测试了化合物抑制肿瘤细胞增殖活性.部分化合物对A-549和Hela肿瘤细胞有弱的细胞毒性,而对BGC-823没有抑制作用,表现出一定的选择性.其中,化合物7ad对A-549有较强的抑制活性(IC50=21.0μmol·L-1),与阳性对照顺铂的抑制活性(IC50=19.4μmol·L-1)相当.初步的构效关系表明化合物的立体结构可能对其抗肿瘤活性影响较大.     

含噻唑烷二酮-3-乙酸结构查尔酮衍生物的合成及抗菌活性的研究

合成了一系列含噻唑烷二酮-3-乙酸结构的新型查尔酮衍生物,并对化合物进行了抗菌活性测定.结果显示,一些化合物对4种多重耐药菌显示出较强的抗菌活性,其中化合物8g,8i,8l和8m在抗耐甲氧西林金黄色葡萄球菌的最小抑制浓度(MIC)达到4μg/mL,与对照药诺氟沙星(norfloxacin)相当.另外,在64μg/mL浓度下,所有化合物对大肠杆菌1356均无明显抑制活性.     

5-对羟基苄基-2,4-噻唑烷二酮的合成

以对甲氧基苯胺为原料,经3步反应合成了胰岛素增敏剂噻唑烷二酮类药物的关键中间体5-(4-羟基苄基)-2,4-噻唑烷二酮,总收率20.4%,其结构经1HNMR确证。     

2,3-二苯基-4-噻唑酮类衍生物的合成及抑菌活性研究

本文以取代苯甲醛、苯胺及巯基乙酸为原料,合成了一系列2,3-二苯基-4-噻唑酮类衍生物,其结构经~1H NMR和MS确证。抑菌活性试验显示,所有目标化合物表现出中等抑菌活性,其中化合物4g对苹果腐烂病菌的抑菌活性最高,能达到62.7%。构效关系研究表明在2,3-二苯基-4-噻唑酮的苯基上引入甲基能增强活性。     

2-(2’,6’-二氯苯基)-1,3-噻唑烷-4-酮衍生物的微波促进合成及抗真菌、 抗肿瘤活性研究

利用微波促进的方法, 以2,6-二氯苯甲醛、胺和巯基乙酸为原料, 合成了系列N-3位不同取代基团的噻唑烷酮衍生物. 部分化合物在Lawesson试剂作用下, 合成了其系列噻唑烷4-硫酮衍生物. 所有化合物通过IR, 1H NMR, MS和元素分析等方法确定结构. 测试了化合物对黄瓜白粉病菌的抑制活性和对宫颈癌细胞的毒性作用, 部分化合物表现出较好的生物活性.     

含1,6-二氢-6-哒嗪酮的1,3,4-噁二唑啉和噻唑烷-4-酮类化合物的合成

以1,6-二氢-6-哒嗪酮-3-甲酰肼(1)与芳香醛反应得到相应的1,6-二氢-6-哒嗪酮-3-羰基芳香醛腙(2a～2e). 再将2a～2e与乙酸酐作用, 合环得到一系列含有1,3,4-噁二唑啉环的衍生物3a～3e; 在DMF中用HSCH₂COOH合环, 得到含有4-噻唑烷酮的衍生物4a～4e. 所有化合物的结构均经元素分析, IR, ¹H NMR 和MS谱得以证实.     

超声辐射下含1,2,3-三唑噻唑烷酮衍生物的合成

采用超声辐射法,以2-苯基-1,2,3-三唑-4-甲酰肼为原料,合成了3-(2-苯基-1,2,3-三唑-4-基)-5H-4-氧代噻唑[2,3-c].1,2,4-三唑,再与各种芳香醛进行Knoevenagel缩合反应,合成了一系列噻唑烷酮衍生物.所有目标化合物结构经元素分析,IR,1H NMR确证.     

2-取代-3-芳基-4-噻唑啉(硫)酮衍生物的合成、晶体结构和生物活性

从2-取代-3-芳基-4-噻唑啉酮(4a～4e和5)合成了三个系列新型噻唑啉酮衍生物, 即5-芳基亚甲基-4-噻唑啉酮(6a～6j), 4-噻唑硫酮(7a～7e和8)和4-氰基亚胺基噻唑烷(11a～11e和12). 中间体4a～4e和5由醛、胺和巯基乙酸缩合得到. 所有化合物的结构均经元素分析和¹H NMR确证, 并且采用X射线单晶衍射分析方法测定了化合物4b的结构. 初步生物活性试验结果表明, 部分标题化合物具有一定的杀菌活性和促进黄瓜子叶生根活性.     

Synthesis and Characterization of New Thiazolidin-4-one Derivatives

The synthesis of some new functionalized thiazolidin-4-one derivatives has been described. The N-substituted-thiosemicarbazides 3a-3i were obtained though the reaction of alkylamines 2a–2i , carbon disulfide, and hydrazine hydrate. The condensation reaction between 3a–3i and 4-amino-2-methanesulfanylpyrimidine-5-carboxaldehyde 1 afforded the thiosemicarbazones 4a–4i . The corresponding thiazolidin-4-ones 5a–5i were prepared by cyclization of 4a–4i with ethyl bromoacetate. The structures of the final products were confirmed by IR, ¹ H NMR, ¹³ C NMR, and HRMS.     

Synthesis of Some Novel 5-(Arylidene)-2-imino-3(pyridin-2-yl)thiazolidin-4-one Derivatives

Treatment of 2-aminopyridine ( 1 ) with chloroacetyl chloride in dry benzene gave 2-chloro-N-(pyridin-2-yl)acetamide ( 3 ), which on further reaction with potassium thiocyanate gave 2-imino-3-(pyridin-2-yl)thiazolidin-4-one ( 4 ) as an intermediate compound for the synthesis of pyridin-2-yl substituted 2-imino-thiazolidine-4-one derivatives. Cyclocondensation reaction of ( 4 ) with a series of aromatic aldehydes gave 5-arylidene derivatives of pyridin-2-yl substituted 2-imino-thiazolidine-4-ones 5a–j . ¹ H and ¹³C NMR spectroscopy, as well as elemental analyses, were used for the identification of these new compounds.     

Synthesis of Novel 2-Iminothiazolidin-4-ones

Abstract

Thiazolidin-4-ones are known to exhibit diverse biological activities such as antimicrobial, anticancer, antidiarrheal, anticonvulsant, antidiabetic, antihistaminic, and antifungal activities. In the present investigation, a series of 2-haloacetamides was prepared by reacting chloroacetyl chloride with amines in dry benzene under reflux conditions. The formed 2-haloacetamides reacted with potassium thiocyanate in refluxing dry acetone to afford new 2-iminothiazolidin-4-ones. The 5-arylidene-2-imino-3 (napthalen-2yl)-thiazolidin-4-ones were prepared by condensing 2-iminothiazolidin-4-ones with substituted benzaldehydes. All the products were characterized by infrared, mass, and ¹H and ¹³C NMR techniques.     

An Efficient and Convenient Protocol for the Synthesis of Thiazolidin-4-Ones

Abstract

Without a catalyst and under solvent-free conditions, 2,3-disubstituted-1,3-thiazolidin-4-one 5a–j derivatives were synthesized efficiently via the three-component reaction of aryl hydrazide, aromatic aldehyde, and mercaptoacetic acid. All the newly synthesized compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy and elemental analysis.

GRAPHICAL ABSTRACT      

A Convenient Synthesis of Thiazolidin-2-ones from Thiazolidine-2-thiones: Antibiotic Activity and Revisiting the Mechanism

Abstract

Various substituted thiazolidin-2-ones were synthesized from the corresponding thiazolidine-2-thiones with bromoethanol in ethanol with sodium ethoxide as a base. The optimal reaction conditions and mechanism were reinvestigated in detail. The bioassay indicated that (S)-4-isobutyl and (S)-4-benzylthiazolidin-2-ones show certain inhibitive activities against Candida albicans and Escherichia coli.

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.

GRAPHICAL ABSTRACT     

Facile Novel Synthesis and Reactions of Thiazolidin-4-one Derivatives for Antimicrobial Agents

A facile and fast procedure for synthesis of 3-phenyl-cyclohexane(1′-2)thiazolidin-4-one (1), which underwent condensation with glucose and p-chlorobenzaldehyde to afford 2 and 3, respectively. Compound 3 was used as precursor for the preparation of some fused heterocyclic compounds 4–7. Compound 4 was alkylated using dichloroacetone and chloroacetic acid to afford 8 and 9, respectively. Also, it reacted with acrylonitrile and hydrazine hydrate to afford 10 and 11, respectively. Compound 9 was condensed with p-chlorobenzaldehyde and glucose to afford 12 and 13, respectively. Selected members of the synthesized compounds were screened for antimicrobial activity.     

Design,Synthesis and Antitumor Activity of Novel Indolin-2-one Derivatives Containing 4-Thiazolidinone Moiety

A series of novel indolin-2-one derivatives containing 4-thiazolidinone moiety(7a―7r) were synthesized and evaluated for their in vitro antitumour activities against MDA-MB-231(human breast cancer), H460(human lung cancer) and HT-29(human colon cancer) cell lines by standard 3-(4,5-dimethylthiazae-2-yl)-2,5-diphenyltetrazo- lium bromide(MTT) assay. Representative compounds(7d, 7k, 7m, 7p) with higher cytotoxicity were further examined against one normal cell line(WI-38, human fetal lung fibroblasts). The preliminary investigation shows that most of the compounds display moderate to excellent potency and high selectivity against different human cancer cell lines. In particular, the most potent compound 7m shows promising cytotoxicity against MDA-MB-231, H460 and HT-29 cell lines with IC₅₀ values of 0.78, 0.056 and 0.018 μmol/L, respectively. The potency is much higher than that of Sunitinib(IC₅₀=3.46 μmol/L against MDA-MB-231, IC₅₀=2.59 μmol/L against H460, IC₅₀=1.50 μmol/L against HT-29) by 4.4, 46.3 and 83.3 fold.