3-取代吲哚衍生物抗肿瘤活性研究进展

吲哚是一种自然界中广泛存在的化合物,具有抗肿瘤、抗氧化、抗菌等生物活性。在吲哚3-位引入不同的取代基,进行结构的修饰与改造一直是药物研究的热点。本文归纳总结了近年来相关的文献,对吡唑及吡唑啉类、二唑及三唑类、与2-位成环类等不同杂环取代的3-取代吲哚衍生物的抗肿瘤活性进行系统性的综述,以期为高活性抗肿瘤药物的研发提供一定的理论基础。     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

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.     

Eu(NTf2)3催化吲哚与醛(酮)反应合成二吲哚基甲烷

二(三氟甲基磺酰)亚胺铕(Ⅲ)[Eu(NTf2)3,Tf=SO2CF3]作催化剂,吲哚与醛(酮)在室温下发生亲电取代反应合成了一系列二吲哚基甲烷,产率85%～98%.该法反应条件温和、时间短、催化剂用量少且可以回收重复使用.     

二氢吲哚-2,3-二酮衍生物抑菌活性研究进展

二氢吲哚-2,3-二酮是一种结构简单且应用广泛的药物小分子,其衍生物的合成、结构和药理活性等备受关注。已有报道表明二氢吲哚-2,3-二酮具有抗菌、抗衰老、降血脂、抗癫痫、抗病毒等多种生物活性。本文主要围绕抑菌生物活性,对国内外关于二氢吲哚-2,3-二酮类化合物的构效关系进行分析总结,为后期该类新型抗菌化合物的设计合成提供参考。     

吲哚-2,3-二酮衍生物抗病毒活性研究进展

吲哚-2,3-二酮是一种广泛存在于天然产物中的化合物,基于其结构特点可以发生不同类型的反应,为其衍生物的合成提供了便利的条件,因此目前其合成和活性的研究备受关注.本文对近年来吲哚-2,3-二酮衍生物抗病毒活性研究情况进行了综述,分别介绍了对HIV、痘病毒、SARS病毒、柯萨奇病毒B3和烟草花叶病毒的抑制活性.重点介绍了吲哚-2,3-二酮衍生物对HIV病毒的作用以及对HIV病毒进入人体破坏人体的免疫功能后容易感染的细菌和结核病的作用.     

5-苯亚甲基-2,4-噻唑二酮的催化合成和紫外光谱的取代基效应

在KF -Al2 O3 负载型固体碱催化下 ,2 ,4-噻唑二酮 1和芳香醛 2a～ 2f发生缩合反应 ,高产率地合成了 5-苯亚甲基 2 ,4-噻唑二酮 3a～ 3f,测定了产物 3a～ 3f在 16种溶剂中的紫外光谱 ,其最大吸收频率与Hammett取化基常数存在良好的线性关系     

E,E-1-(3＇-吲哚基)-5-取代苯基-1,4-戊二烯-3-酮化合物的合成及抗炎活性

戊二烯酮化合物;E;E-1-(3＇-吲哚基)-5-取代苯基-1;4-戊二烯-3-酮化合物的合成及抗炎活性     

2,5-二取代吲哚衍生物的合成及抗增殖活性研究

以对硝基苯肼为起始原料,采用费舍尔吲哚合成法合成中间体5-硝基吲哚-2-羧酸酯(3),经还原合成5-氨基吲哚-2-羧酸酯(4),再与4-甲氧基-2-甲苯基异氰酸酯合成脲(5),(5)在水合肼作用下5-(3-(4-甲氧基-2-甲苯基)脲基)-1H-吲哚-2-碳酰肼(6),化合物6和取代醛反应,合成了6个2,5-二取代吲哚衍生物(7a～7f),其结构经~1HNMR,~(13)CNMR和HR-MS表征。采用MTT法研究了7a～7f对人肺癌细胞(A549)和人肝癌细胞(HepG-2)的体外抗增殖活性。结果显示:7d体外抑制活性最优,其IC_(50)分别为10.35μmol·L~(-1)、12.60μmol·L~(-1)。     

无溶剂、无催化剂条件下5-[(3-吲哚基)-芳甲基]-2,2-二甲基- 1,3-二氧六环-4,6-二酮的合成

在无溶剂和催化剂条件下,由芳香醛、吲哚、丙二酸亚异丙酯的三组分缩合反应,制备了5-[(3-吲哚基)-芳甲基]-2,2-二甲基-1,3-二氧六环-4,6-二酮,产率为70%～85%,产物结构经1H NMR,IR确证.     

3-Aryl-5-[(aryloxy)methyl]-3-[(1H-1,2,4-triazol-1-yl)methyl]-2-methylisoxazolidine derivatives. Synthesis and antifungal activity

The synthesis and antifungal activity of a novel series of 3-aryl-5-[(aryloxy)methyl]-3-[(1H-1,2,4-triazol-1-yl)-methyl]-2-methylisoxazolidines are described. The in vitro activity was evaluated in solid agar cultures against a variety of dermatophytes and yeast fungi, while in vivo activity was measured in an immune-compromised mouse model of systemic candidiasis. The activity of the title series was compared to that of ketoconazole and one derivative, the cis-3-(4-chlorophenyl)-5-(4-chlorophenyloxy)methyl analogue 5f was found to possess a similar potency in the in vivo assay. Structure-activity relationship correlations are also discussed.     

Synthesis,anti-hyperglycaemic activity,and in-silico studies of N-substituted 5-(furan-2-ylmethylene)thiazolidine-2,4-dione derivatives

Thiazolidinedione derivatives have been used as anti-hyperglycemic agents in diabetic patients since last decade. In the present study, a series of N-substituted-5-(furan-2-ylmethylene)thiazolidine-2,4-dione derivatives were synthesized and characterized by ¹H-NMR, ¹³C-NMR and mass spectra. The introduction of the alkyl/haloalkyl moiety onto the amidic nitrogen of the thiazolidine-2,4-dione ring was intended to enhance the anti-hyperglycaemic activity, which was further tested in vivo by using alloxan-induced diabetic laca mice. Molecular docking simulation studies further helped in understanding the nature of the interactions and the binding mode of ligands inside the active site of the protein tyrosine phosphatase 1B enzyme, which negatively regulates the insulin signaling pathway. The compounds were screened for in-vivo anti-hyperglycaemic activity in which compounds 9 and 10 have exhibited significant decreases in blood glucose level comparable to that of pioglitazone.

     

L-Proline-Catalyzed Synthesis of Novel 5-(1H-Indol-3-yl-methylene)-thiazolidine-2,4-dione Derivatives as Potential Antihyperglycemic Agents

Knoevenagel condensation between indole-3-aldehyde 1 and an active methylene group containing 2,4-thiazolidinedione 2 in refluxing toluene using L-proline as a catalyst yielded 3, which on alkylation using 2 equivalents of alkylating agent under phase-transfer-catalyzed (PTC) conditions using K₂CO₃ as a base in dimethylformamide gave N,N^I-symmetrically disubstituted 5-(1H-indol-3ylmethylene)-thiazolidine-2,4-diones 4. Alternately, 4 can be synthesized by condensing 5 and 6 in a single step. Using this synthetic strategy, N,N^I-unsymmetricallydisubstituted derivatives 9a–f were prepared either by condensing 6 with N-substituted-2,4-thiazolidinedione 5 to obtain 7 followed by alkylation under PTC conditions or condensing 6 with N-unsubstituted- 2,4-thiazolidinedione 2 to yield 8 followed by alkylation under PTC conditions. The latter are the dehydro analogs of the dihydro-N-substituted-5-(1H-indol-3-yl-methylene)-thiazolidine-2,4-diones, which are potential antihyperglycemic agents.

Synthesis and bioactivity of novel 3-(1-hydroxyethylidene)-5-substituted-pyrrolidine-2,4-dione derivatives

Ten novel 5-substituted derivatives of 3-(l-hydroxyethylidene)pyrrolidine-2,4-dione were synthesized.The compounds were confirmed by IR,:H NMR,MS and elemental analysis.The bioassay indicated that these compounds showed noticeable herbicidal activities,and compounds 6f and 6j exhibited excellent inhibitory activities against the stalk of Echinochloa crusgalli,with EC50 values of 94.4 and 72.7 mg/L,respectively.     

5-(1H-Indol-3-yl)-pyrazolyl derivatives as colorimetric sensor for anions

The synthesis, characterisation and binding and deprotonation studies with anions for four 5-(1H-indol-3-yl)-pyrazolyl derivatives (2–5) have been described. It is worthy to mention that sensor 2 shows a drastic change in absorption spectrum (ca. 335 nm) and colour (colourless to blue) upon addition of F^? in DMSO solution due to the deprotonation of indole –NH proton, as confirmed by ¹H NMR titration. Sensor 4 recognizes F^? and CN^? ions by deprotonation mechanism with visible colour change of the solution in a similar manner to that of 2. However, in contrary to 2 and 4, sensor 3 binds with F^?, CN^?, H₂PO₄ ^?, AcO^? and PhCOO^? ions exploiting hydrogen-bonding interaction with the shifting of absorption band to longer wavelength and subsequent colour change of the solution. Compound 5 recognizes F^? without any visual colour change and its binding is studied by ¹H NMR titration to acquire the important information about the nature of binding between F^? and 5.     

Synthesis of 5-(thiazol-5-yl)-4,5-dihydroisoxazoles from 3-chloropentane-2,4-dione

Condensation of 3-chloropentane-2,4-dione with thioamides gives 1-(thiazol-5-yl)ethanones and subsequent Wittig olefination, followed by nitrile oxide 1,3-dipolar cycloaddition to the resulting prop-1-en-2-yl moiety, delivers racemic 5-(thiazol-5-yl)-4,5-dihydroisoxazoles. When this thiazole and isoxazoline diheterocyclic scaffold has a carboethoxy substituent at C2 of the thiazole ring, aminolysis provides for effective diversification. A 50-member library of various 5-(thiazol-5-yl)-4,5-dihydroisoxazoles is reported.     

Synthesis of N-methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine

N-Methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine (1)(1) is a key intermediate in the preparation of premafloxacin (2), which was under development as an antibiotic for use against pathogens of veterinary importance. This paper describes the development of a practical, efficient, and stereoselective process for the preparation of 1 from isobutyl (3S)-3-[methyl[(1S)-1-phenylethyl]amino]butanoate (5c). The key steps in the synthetic sequence are an asymmetric Michael addition, which yields 5c, and a stereoselective alkylation, which yields (3S,4S)-3-allyl-1,4-dimethylazetidin-2-one (17).