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Catalyst-free synthesis of highly biologically active 5-arylidene rhodanine and 2,4-thiazolidinedione derivatives using aldonitrones in polyethylene glycol. 在聚乙二醇中使用醛丙酮无催化剂合成高生物活性的5-芳基罗丹宁和2,4-噻唑烷二酮衍生物。
Pub Date : 2013-01-01 Epub Date: 2013-02-14 DOI: 10.1155/2013/273534
Dhruva Kumar, Suresh Narwal, Jagir S Sandhu

A green, efficient synthesis of 5-arylidene rhodanine and 2,4-thiazolidinedione derivatives without using any external catalyst in polyethylene glycol (PEG) at 80°C has been described. Reaction procedure is very simple, short, and obtained yields are very high.

在80°C的聚乙二醇(PEG)中,不使用任何外部催化剂,绿色高效地合成了5-芳基罗丹宁和2,4-噻唑烷二酮衍生物。反应过程简单,反应时间短,所得收率高。
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引用次数: 3
Synthesis and In Vitro Antimicrobial Evaluation of New 1,3,4-Oxadiazoles Bearing 5-Chloro-2-methoxyphenyl Moiety. 含5-氯-2-甲氧基苯基基团的新型1,3,4-恶二唑的合成及体外抗菌评价
Pub Date : 2013-01-01 Epub Date: 2013-03-31 DOI: 10.1155/2013/725673
Basavapatna N Prasanna Kumar, Kikkeri N Mohana, Lingappa Mallesha, Kikkeri P Harish

A series of new 1,3,4-oxadiazole derivatives, 4(a-h), containing 5-chloro-2-methoxy benzohydrazide moiety were synthesized by the reaction of 5-chloro-2-methoxybenzoate with different aromatic carboxylic acids. These newly synthesized compounds were characterized by FT-IR, (1)H NMR, mass spectra, and also by elemental analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Antimicrobial studies revealed that compounds 4c, 4f, and 4g showed significant activity against tested strains.

以5-氯-2-甲氧基苯甲酸为原料,与不同的芳香羧酸反应,合成了一系列含有5-氯-2-甲氧基苯并肼的1,3,4-恶二唑衍生物4(A -h)。这些新合成的化合物通过FT-IR, (1)H NMR,质谱和元素分析进行了表征。对所有新合成的化合物进行了抗菌和抗真菌活性筛选。抗菌研究表明,化合物4c、4f和4g对试验菌株具有显著的活性。
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引用次数: 6
Synthesis and evaluation of some novel chromone based dithiazoles as antimicrobial agents. 新型铬基二噻唑类抗菌药物的合成与评价。
Pub Date : 2013-01-01 Epub Date: 2013-11-27 DOI: 10.1155/2013/815453
Naureen Aggarwal, Vishal Sharma, Harpreet Kaur, Mohan Paul Singh Ishar

Novel substituted 1,2,4-dithiazolylchromones 3a-j were synthesized by the reaction of 3-formylchromones (1a-j) with two equivalents of p-chlorothiobenzamide (2) in dry xylene and characterized spectroscopically (IR, (1)H and (13)C NMR, mass) and elemental analysis. All synthesized compounds were screened for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains and were found to possess good to moderate inhibitory potential against all tested strains. Antimicrobial results reveal that compounds bearing lipophilic electron withdrawing groups such as chloro and bromo displayed significant inhibitory potential against both bacterial and fungal strains. Particularly, compound 3c displayed significant inhibitory against bacterial strains and compound 3h exhibits significant inhibitory potential in comparison to standard drug fluconazole against fungal strain S. cerevisiae.

以3-甲酰基chromones (1a-j)与对氯硫苯酰胺(2)在干二甲苯中反应合成了新型取代的1,2,4-二噻唑基chromones 3a-j,并通过IR, (1)H和(13)C NMR,质量和元素分析对其进行了表征。所有合成的化合物对各种病原菌和真菌菌株的体外抗菌活性进行了筛选,发现对所有测试菌株具有良好到中等的抑制潜力。抗菌结果表明,含有亲脂性吸电子基团(如氯和溴)的化合物对细菌和真菌菌株都有显著的抑制潜力。特别是,化合物3c对细菌菌株表现出显著的抑制作用,化合物3h与标准药物氟康唑相比,对酿酒葡萄球菌真菌菌株表现出显著的抑制潜力。
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引用次数: 7
Microwave-assisted synthesis and biological evaluation of dihydropyrimidinone derivatives as anti-inflammatory, antibacterial, and antifungal agents. 微波辅助合成及抗炎、抗菌和抗真菌二氢嘧啶衍生物的生物学评价。
Pub Date : 2013-01-01 Epub Date: 2013-04-15 DOI: 10.1155/2013/197612
Anjna Bhatewara, Srinivasa Rao Jetti, Tanuja Kadre, Pradeep Paliwal, Shubha Jain
A simple protocol for the efficient preparation of aryl and heteroaryl substituted dihydropyrimidinone has been achieved via initial Knoevenagel, subsequent addition, and final cyclization of aldehyde, ethylcyanoacetate, and guanidine nitrate in the presence of piperidine as a catalyst in solvent-free under microwave irradiation. The synthesized compounds showed a good anti-inflammatory, antibacterial, and antifungal activity.
在无溶剂微波照射下,以哌啶为催化剂,通过初始Knoevenagel,随后加成,最后将醛、氰乙酸乙酯和硝酸胍环化,获得了一种简单的制备芳基和杂芳基取代二氢嘧啶酮的方法。合成的化合物具有良好的抗炎、抗菌和抗真菌活性。
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引用次数: 12
Recent pharmacological developments on rhodanines and 2,4-thiazolidinediones. 罗丹宁和 2,4-噻唑烷二酮类化合物的最新药理学发展。
Pub Date : 2013-01-01 Epub Date: 2013-05-02 DOI: 10.1155/2013/793260
Ravinder Singh Bhatti, Sakshi Shah, Suresh, Pawan Krishan, Jagir S Sandhu

Thiazolidines are five-member heterocyclic having sulfur, nitrogen, and oxygen atoms in their ring structure and exhibiting potent as well as wide range of pharmacological activities. In this minireview, recent updates on synthesis and pharmacological evaluations of molecules based on 2,4-thiazolidine and rhodanine are discussed.

噻唑烷类是五元杂环化合物,其环状结构中含有硫、氮和氧原子,具有强效和广泛的药理活性。在这篇微型综述中,将讨论基于 2,4-噻唑烷和罗丹宁的分子的合成和药理评估的最新进展。
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引用次数: 0
In Silico Inhibition Studies of Jun-Fos-DNA Complex Formation by Curcumin Derivatives. 姜黄素衍生物对Jun-Fos-DNA复合物形成的硅抑制研究。
Pub Date : 2012-01-01 Epub Date: 2012-12-06 DOI: 10.1155/2012/316972
Anil Kumar, Utpal Bora

Activator protein-1 (AP1) is a transcription factor that consists of the Jun and Fos family proteins. It regulates gene expression in response to a variety of stimuli and controls cellular processes including proliferation, transformation, inflammation, and innate immune responses. AP1 binds specifically to 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element 5'-TGAG/CTCA-3' (AP1 site). It has been found constitutively active in breast, ovarian, cervical, and lung cancers. Numerous studies have shown that inhibition of AP1 could be a promising strategy for cancer therapeutic applications. The present in silico study provides insights into the inhibition of Jun-Fos-DNA complex formation by curcumin derivatives. These derivatives interact with the amino acid residues like Arg155 and Arg158 which play a key role in binding of Jun-Fos complex to DNA (AP1 site). Ala151, Ala275, Leu283, and Ile286 were the residues present at binding site which could contribute to hydrophobic contacts with inhibitor molecules. Curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked.

激活蛋白1 (Activator protein-1, AP1)是一种由Jun和Fos家族蛋白组成的转录因子。它调节基因表达以应对各种刺激,并控制细胞过程,包括增殖、转化、炎症和先天免疫反应。AP1特异结合12- o - tetradecanoylphorol -13-acetate (TPA)响应元件5'-TGAG/CTCA-3' (AP1位点)。它已被发现在乳腺癌、卵巢癌、宫颈癌和肺癌中具有组成性活性。大量研究表明,抑制AP1可能是一种很有前途的癌症治疗策略。目前的硅研究提供了姜黄素衍生物抑制Jun-Fos-DNA复合物形成的见解。这些衍生物与Arg155和Arg158等氨基酸残基相互作用,这些氨基酸残基在Jun-Fos复合物与DNA (AP1位点)的结合中起关键作用。Ala151、Ala275、Leu283和Ile286是存在于结合位点的残基,可以促进与抑制剂分子的疏水接触。硫酸姜黄素被认为是所有天然姜黄素衍生物中最有效的抑制剂。
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引用次数: 7
Room temperature synthesis and antibacterial activity of new sulfonamides containing n,n-diethyl-substituted amido moieties. 含n,n-二乙基取代氨基的新型磺胺类化合物的室温合成及其抗菌活性。
Pub Date : 2012-01-01 Epub Date: 2012-10-17 DOI: 10.1155/2012/367815
Olayinka O Ajani, Oluwole B Familoni, Feipeng Wu, Johnbull O Echeme, Zheng Sujiang
Sulfonamide drugs which have brought about an antibiotic revolution in medicine are associated with a wide range of biological activities. We have synthesized a series of α-tolylsulfonamide, 1–11 and their substituted N,N-diethyl-2-(phenylmethylsulfonamido) alkanamide derivatives, 12–22 in improved and excellent yields in aqueous medium at room temperature through highly economical synthetic routes. The chemical structures of the synthesized compounds 1–22 were confirmed by analytical and spectral data such as IR, 1H- and 13C-NMR, and mass spectra. The in vitro antibacterial activity of these compounds along with standard clinical reference, streptomycin, was investigated on two key targeted organisms. It was observed that 1-(benzylsulfonyl)pyrrolidine-2-carboxylic acid, 2 emerged as the most active compound against Staphylococcus aureus at MIC value of 1.8 μg/mL while 4-(3-(diethylamino)-3-oxo-2-(phenylmethylsulfonamido) propyl)phenyl phenylmethanesulfonate, 22 was the most active sulfonamide scaffold on Escherichia coli at MIC value of 12.5 μg/mL.
磺胺类药物引起了医学上的抗生素革命,它与广泛的生物活性有关。通过经济的合成路线,在室温条件下,以较好的收率合成了一系列α-甲磺酰胺、1-11及其取代的N,N-二乙基-2-(苯基甲基磺酰胺)烷酰胺衍生物、12-22。合成的化合物1-22的化学结构通过IR、(1)H-和(13)C-NMR以及质谱等分析和光谱数据得到了证实。研究了这些化合物与标准临床参考链霉素对两种关键目标生物的体外抗菌活性。结果表明,1-(苄基磺酰基)吡咯烷-2-羧酸,2对金黄色葡萄球菌的抑制活性最高,MIC值为1.8 μg/mL; 4-(3-(二乙胺)-3-氧基-2-(苯基甲基磺酰胺)丙基)苯基苯基甲基甲磺酸,22对大肠杆菌的抑制活性最高,MIC值为12.5 μg/mL。
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引用次数: 8
Synthesis and biological evaluation of achiral indole-substituted titanocene dichloride derivatives. 非手性吲哚取代二氯化二茂钛衍生物的合成及生物学评价。
Pub Date : 2012-01-01 Epub Date: 2012-06-12 DOI: 10.1155/2012/905981
Anthony Deally, Frauke Hackenberg, Grainne Lally, Matthias Tacke

Six new titanocene compounds have been isolated and characterised. These compounds were synthesised from their fulvene precursors using Super Hydride (LiBEt3H) followed by transmetallation with titanium tetrachloride to yield the corresponding titanocene dichloride derivatives. These complexes are bis-[((1-methyl-3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride (5a), bis-[((5-methoxy-1-methyl,3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride (5b), bis-[((1-methyl,3-diethylaminomethyl)indol-4-yl)methylcyclopentadienyl] titanium (IV) dichloride (5c), bis-[((5-bromo-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5d), bis-[((5-chloro-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5e), and bis-[((5-fluoro-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5f). All six titanocenes 5a-5f were tested for their cytotoxicity through MTT-based in vitro tests on CAKI-1 cell lines using DMSO and Soluphor P as solubilising agents in order to determine their IC50 values. Titanocenes 5a-5f were found to have IC50 values of 10 (±2), 21 (±3), 29 (±4), 140 (±6), and 450 (±10) μM when tested using DMSO.

六个新的二茂钛化合物已被分离和表征。这些化合物是用超氢化物(LiBEt3H)从它们的fulveni前体合成的,然后与四氯化钛金属化,得到相应的二氯化二茂钛衍生物。这些配合物是双-[(1-甲基-3-二乙基氨基甲基)吲哚-2-基)甲基环戊二烯基]钛(IV)二氯(5a),双-[((5-甲氧基-1-甲基,3-二乙基氨基甲基)吲哚-2-基)甲基环戊二烯基]钛(IV)二氯(5b),双-[((1-甲基,3-二乙基氨基甲基)吲哚-4-基)甲基环戊二烯基]钛(IV)二氯(5c),双-[((5-溴-1-甲基)吲哚-3-基)甲基环戊二烯基]钛(IV)二氯(5d),双-[(5-氯-1-甲基)吲哚-3-基)甲基环戊二烯基]二氯化钛(5e)和双-[(5-氟-1-甲基)吲哚-3-基)甲基环戊二烯基]二氯化钛(5f)。采用DMSO和Soluphor P作为增溶剂,对CAKI-1细胞系进行了基于mtt的体外细胞毒性测试,以确定所有六种钛茂烯5a-5f的IC50值。通过DMSO测试,发现钛茂烯5a-5f的IC50值分别为10(±2)、21(±3)、29(±4)、140(±6)和450(±10)μM。
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引用次数: 4
Pharmacophore Modelling and 3D-QSAR Studies on N(3)-Phenylpyrazinones as Corticotropin-Releasing Factor 1 Receptor Antagonists. 促肾上腺皮质激素释放因子1受体拮抗剂N(3)-苯吡嗪酮的药效团建模和3D-QSAR研究。
Pub Date : 2012-01-01 Epub Date: 2012-05-31 DOI: 10.1155/2012/452325
Paramjit Kaur, Vikas Sharma, Vipin Kumar

Pharmacophore modelling-based virtual screening of compound is a ligand-based approach and is useful when the 3D structure of target is not available but a few known active compounds are known. Pharmacophore mapping studies were undertaken for a set of 50 N(3)-phenylpyrazinones possessing Corticotropin-releasing Factor 1 (CRF 1) antagonistic activity. Six point pharmacophores with two hydrogen bond acceptors, one hydrogen bond donor, two hydrophobic regions, and one aromatic ring as pharmacophoric features were developed. Amongst them the pharmacophore hypothesis AADHHR.47 yielded a statistically significant 3D-QSAR model with 0.803 as R (2) value and was considered to be the best pharmacophore hypothesis. The developed pharmacophore model was externally validated by predicting the activity of test set molecules. The squared predictive correlation coefficient of 0.91 was observed between experimental and predicted activity values of test set molecules. The geometry and features of pharmacophore were expected to be useful for the design of selective CRF 1 receptor antagonists.

基于药效团模型的化合物虚拟筛选是一种基于配体的方法,在不知道靶标三维结构但已知少量活性化合物的情况下非常有用。对一组具有促肾上腺皮质激素释放因子1 (CRF 1)拮抗活性的50种N(3)-苯吡嗪酮进行药效团定位研究。开发了具有2个氢键受体、1个氢键供体、2个疏水区和1个芳香环为药效特征的6点药效团。其中药效团假说aadhrr .47产生的3D-QSAR模型具有统计学意义,R(2)值为0.803,被认为是最佳药效团假说。建立的药效团模型通过预测测试集分子的活性进行了外部验证。试验集分子的实验活度值与预测活度值的平方预测相关系数为0.91。药效团的几何形状和特征有望为选择性crf1受体拮抗剂的设计提供依据。
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引用次数: 15
Identification of a Novel Series of Potent TrkA Receptor Tyrosine Kinase Inhibitors. 一种新型TrkA受体酪氨酸激酶抑制剂的鉴定。
Pub Date : 2012-01-01 Epub Date: 2012-05-02 DOI: 10.1155/2012/412614
Stéphane L Raeppel, Frédéric Gaudette, Hannah Nguyen, Normand Beaulieu, James Wang, Christiane Maroun, Jeffrey M Besterman, Arkadii Vaisburg

A novel series of N-(3-(6-substituted-aminopyridin-3-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting TrkA receptor tyrosine kinase was identified. SAR study of the series allowed us to design and synthesize compounds possessing inhibitory activity of TrkA kinase enzyme in the low nanomolar range with low residual activity against c-Met and with no significant activity against VEGFR2.

鉴定了一系列靶向TrkA受体酪氨酸激酶的N-(3-(6-取代-氨基吡啶-3-基氧基)苯基)-2-氧-3-苯基咪唑烷-1-羧酰胺。该系列的SAR研究使我们能够设计和合成具有低纳摩尔范围的TrkA激酶抑制活性的化合物,对c-Met的残留活性低,对VEGFR2没有明显的活性。
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引用次数: 4
期刊
International Journal of Medicinal Chemistry
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