A convenient [hydroxy(tosyloxy)iodo]benzene-mediated one-pot synthesis of 2-arylimidazo[2,1-b]benzothiazoles

Several 2-arylimidazo[2,1-b]benzothiazoles (4) have been conveniently synthesized in one-pot reactions via α-tosyloxylation of enolizable ketones (1) using [hydroxy(tosyloxy)iodo]benzene 2 in acetonitrile, followed by treatment with 2-amino-6-(substituted)benzothiazoles (3). The present protocol offers several advantages towards general access of 2-arylimidazo[2,1-b]benzothiazoles, including an intriguing alternative to the literature protocols, a readily available nontoxic reagent, operational simplicity and an environmentally benign procedure.     

6-甲基-2-苯基咪唑[2,1-b]并-1,3,4-噻二唑-5-N'-取代苯基亚甲基碳酰肼的设计与合成

根据已有的具有抗肿瘤活性的咪唑[2,1-b]并-1,3,4-噻二唑类化合物的结构及其构效关系,以2-氨基-5-苯基-1,3,4-噻二唑和溴代乙酰乙酸乙酯为原料设计并合成了8个6-甲基-2-苯基咪唑[2,1-b]并-1,3,4-噻二唑-5-碳酰肼的腙类衍生物.通过1HNMR、LC-MS、IR等方法对其结构进行了确证.     

质子泵抑制剂的合成研究

胃酸被认为是消化性溃疡的最主要致病因素之一,无论手术治疗还是药物治疗,减少胃酸分泌都是促进溃疡愈合的最常用手段。质子泵抑制剂是一类新型的抑制胃酸分泌的药物。该文叙述了质子泵抑制剂及关键中间体2-巯基苯并咪唑化合物、2-巯基咪唑并[4,5-b]吡啶化合物、2-氯甲基吡啶化合物的合成研究概况,探讨了质子泵抑制剂的较佳合成方案和结构设计思路。     

Synthesis of imidazo[2,1-b]thiazoles through the reaction of thiohydantoins and α-bromoketones

Imidazo-fused heterocycles are used as anticancer agents. In this study, some novel imidazo[2,1-b]thiazoles were synthesized from thiohydantoins and α-bromoketones in good yields. This method has the advantages of simple operation, high yields, and mild reaction conditions and uses less toxic and low-cost chemical reagents.     

Facile and Selective Synthesis of Imidazobenzimidazoles via a Copper‐Catalysed Domino Addition/Cycloisomerisation/ Coupling Process

A copper(I)‐catalysed domino transformation for the synthesis of tricyclic imidazobenzimidazole derivatives was developed. Using readily available primary propargylic amines and o‐haloarylcarbodiimides as the starting materials, a variety of substituted benzo[d]imidazo[1,2‐a]imidazoles was efficiently and selectively assembled. Further investigations indicated that the domino reaction was likely the result of a novel addition/cycloisomerisation/coupling process.

     

Synthesis of Highly Substituted Imidazo[1,5‐a]quinoxalines Through a Multicomponent Reaction Followed by Deprotection–Cyclization

An operationally simple and efficient, one‐pot, two‐step methodology has been developed for the assembly of medicinally important imidazo[1,5‐a]quinoxalines. The protocol involves the multicomponent reaction of aryl aldehydes, ortho‐N‐Boc‐phenylenediamines and azidochalcones in the presence of erbium triflate as a Lewis acid catalyst, followed by deprotection–cyclization with 10% trifluoroacetic acid, furnishing the desired compounds in moderate to good yields. By virtue of their convergence, two aromatic rings and four new bonds are generated during the course of this reaction protocol. The structure of one of the compounds was proved by X‐ray crystallography.

     

Synthesis of 4-substituted imidazo[1,2-a]quinoxalines

A concise approach to 4-substituted imidazo[1,2-a]quinoxalines 7 is described, starting from 1-fluoro-2-nitrobenzene ( 3 ). The high variability in the functionalization of the imidazo [1,2-a]quinoxaline-4-position is due to the easy introduction of these substituents by N-acylation in the second last step.     

咪唑[1,2-d]并-1,2,3,4-噻三唑衍生物的合成

为寻找CDC25B磷酸酯酶抑制剂,设计、合成咪唑[1,2-d]并-1,2,3,4-噻三唑衍生物。以溴代乙酰乙酸乙酯和5-氨基-1,2,3,4-噻三唑为原料,经过关环、肼解、缩合3步反应合成了5个目标化合物。通过元素分析、IR、1HNMR和MS分析确定了其结构。活性结果表明,6-甲基咪唑[1,2-d]并-1,2,3,4-噻三唑-5-甲酰肼和N'-苄基-6-甲基咪唑并[1,2-d]并-1,2,3,4-噻三唑-5-甲酰肼对CDC25B有一定的抑制作用。     

二茂铁基咪唑并[1,2-a]吡啶化合物的合成及抗氧化性能

以乙醇为溶剂，在加热条件下采用LaCl3催化2-氨基吡啶、二茂铁甲醛和异氰之间的Groebke-Blackburn-Bienaym?三组分反应（GBB-3CR）合成5个二茂铁基咪唑并[1,2-a]吡啶化合物。利用核磁共振氢谱（proton magnetic resonance，1H NMR）、核磁共振碳谱（carbon-13 magnetic resonance，13C NMR）和超高效液相色谱-电喷雾离子源质谱联用仪（ultra high performance liquid chromatograph electrospray ion source mass spectrometer，UHPLC-ESI-MS）对合成产物结构进行了表征，并通过抑制HO?和还原型谷胱甘肽自由基(glutathione，GS?)引发的DNA氧化反应体系对化合物的抗氧化活性进行了检测，采用淬灭2,2?-偶氮-双-(3-乙基苯并噻唑啉-6-磺酸)二铵盐自由基（2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical，ABTS?）和二苯苦味酰肼自由基（2,2’-diphenyl-1-picrylhydrazyl，DPPH?）体系探索了化合物还原自由基的能力，进而探究了取代基对二茂铁基咪唑并[1,2-a]吡啶抗化合物氧化性能的影响。结果表明：5个目标化合物不仅能够有效地抑制自由基引发的DNA氧化反应，也能捕获自由基，是一类潜在的抗氧化剂。其中，在抑制HO?引发的DNA氧化反应体系中，5个化合物相对空白TBARS吸光度百分数可达65.4%~93.7%；在抑制GS?引发的DNA氧化反应体系中，5个化合物相对空白TBARS吸光度百分数可达25.6%~62.5%；5个二茂铁基咪唑并[1,2-a]吡啶化合物均能够捕获ABTS?和DPPH?两种自由基；双二茂铁基化合物VI抑制自由基引发的DNA氧化反应活性和捕获自由基能力优于其它化合物。     

水相介质下碘催化合成咪唑并[1,2-α]吡啶

以水作为溶剂、分子碘作为催化剂,70℃下,芳香醛、2-氨基吡啶、苯乙炔"一锅法"合成标题化合物.该反应条件温和,所得咪唑并[1,2-α]吡啶衍生物收率可达70％～85％.     

Synthetic access to imidazo[2,1-b]thiazoles

The current review article represents a survey covering the synthetic strategies leading to imidazo[2,1-b]thiazoles since 1980. The review is classified according to nature of starting precursor either 2-aminothiazoles or 2-mercaptothiazoles.     

Reaction of alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5,5-diaryl thiohydantoins. Synthesis of functionalized imidazo[2,1-b][1,3]thiazines

The reaction of stoichiometric amounts of dialkyl acetylenedicarboxylates with alkyl isocyanides in the presence of 5,5-diaryl thiohydantoins afforded imidazo[2,1-b][1,3]thiazines in good overall yields.     

7-羟甲基咪唑并[1,2-a]吡啶的合成

以6-氨基-3-吡啶甲酸为起始原料,经过酯化反应、环合反应、还原反应得到7-羟甲基咪唑并[1,2-a]吡啶,总收率为42％.     

咪唑并[1,2-a]吡啶化合物的简便合成

以2-氨基-3-羟基吡啶为原料,经过一锅两步反应合成了12个咪唑并[1,2-a]吡啶类化合物。2-氨基-3-羟基吡啶与N,N-二甲基甲酰胺二甲基缩醛进行反应,几乎定量得到(E)-N'-(3-羟基吡啶-2-基)-N,N-二甲基甲脒中间体,然后在Na HCO3作用下,于一锅中和活泼亲电化合物(溴乙酸乙酯、溴乙腈和2-溴代苯乙酮)发生合成咪唑环的反应及羟基上的取代反应,以50.3%~85.2%的总收率得到目标产物。该一锅两步方法具有原料易得、反应时间短、操作简便、收率高等优点。     

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC₅₀ values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.     

1,2,4—三唑[3,4,—b]苯并噻唑的合成

首次以ＰＯＣ１３为环合剂环化苯并噻唑腙,合成了３位取代的１,２,４三唑「３,４－ｂ」苯并噻唑,并提出了合理的反庆历程。     

Spray-dried hydroxyapatite-5-Fluorouracil granules as a chemotherapeutic delivery system

This study describes the preparation and characterization of hydroxyapatite-5-Fluorouracil (5FU) granules, which are intended to be used as chemotherapeutic delivery matrices and bone regeneration templates. Suspensions of hydroxyapatite (Hap) nanoparticles in 5FU solution are spray dried as micro sized granules having donut type shape. Several spray drying temperatures are studied 80 °C being the optimized condition for obtaining granules composed by Hap and 5FU without secondary phases. The produced granules at 80 °C reveal a fast releasing rate of 5FU when soaked in buffer phosphate solution maintained at physiological temperature (37 °C), thereby indicating the potential application of the produced Hap matrices for drug delivery systems (DDSs).     

Copper‐Catalyzed Domino Synthesis of Benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones using Cyanamide as a Building Block

An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.

     

[6,7]‐Heterocycle‐Fused 14‐Hydroxymorphinan Derivatives: Design,Synthesis, and Opioid Receptor Activity

A series of new 14‐hydroxymorphinan analogues with a thiazole or imidazo[2,1‐b]thiazole fragment as the heterocyclic function fused to ring C were designed and synthesized. These compounds can be viewed as the result of a direct modification at ring C of the 14‐hydroxymorphinan scaffold. Among these compounds, three were identified as having potent binding affinity (～1 nM ) at both κ and μ receptors, and acting as agonists at κ and partial agonists or antagonists at μ receptors. In view of the promising results from studies on compounds with mixed κ and μ receptor activities, these new compounds warrant further investigation.     

Copper‐Catalyzed Synthesis of Imidazo[1,2‐a]pyridines through Tandem Imine Formation‐Oxidative Cyclization under Ambient Air: One‐Step Synthesis of Zolimidine on a Gram‐Scale

A new copper‐catalyzed oxidative cyclization via C H amination between 2‐aminopyridines and methyl aryl/heteroaryl ketones has been developed under ambient air. Imidazo[1,2‐a]pyridines containing a wide range of functional groups have been synthesized from basic and easily available starting materials. This simple, one‐pot reaction protocol is applicable for the direct preparation of zolimidine (a marketed antiulcer drug) on a large scale.