The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given

Research on the International Development Trend of Big Data and Digital Economy and Its Reference to China

With the wide application and development of big data, digital economy has become the innovation power of global economic growth and has an important impact on the development of global social and economic cooperation. From an international perspective, this paper analyzes the development trend and achievements of the United States, the European Union and important international organizations in the field of digital economy. On this basis, this paper analyzes the current situation and challenges of the development of China's digital economy, and puts forward suggestions and measures to promote the development of China's digital economy in view of the digital gap, value assessment, development mode, talent training

Expression of IFN-γ, IL-1α, NGF-β and TNF-α during the development of cerebellar cortex of Western Anhui white goose

The strep avidin-biotin-peroxidase complex (SABC) immunohistochemical methods were applied to investigate the localization and semi-quantitative distribution of IFN-γ, IL-1α, NGF-β and TNF-α-immunoreactive cells in the cerebellar cortex of Western Anhui white goose at embryonic day 13, 19, 24, 28 (E13, E19, E24, E28) and postnatal day 7, 15 (P7, P15). The possible roles of IFN-γ、IL-1α、NGF-β and TNF-α in the development of cerebellar cortex were discussed. The results indicated that in the external granular layer, there were IFN-γ and TNF-α positive cells at E13, E19, E24, E28, P7, IL-1α positive cells at E13, E19, E24, E28 and NGF-β positive cells at E13, E19 , E24. The expression levels of these four cytokines all reached peaks at E19 of the six tested periods in this study. In the Purkinje cell layer, there were IFN-γ, IL-1α and TNF-α positive cells at E13, E19, E24, E28, P7, P15 and NGF-β positive cells at E13, E19, E24, E28, P7. In the internal granular layer, there were IFN-γ positive cells at E13, E19, E24, E28, P7, P15, IL-1α and TNF-α positive cells at E13, E19, E24, E28, P7 and NGF-β positive cells at E13, E19, E24, E28. These results showed that E19 might be the “critical stage” in the cerebellar cortex development of Western Anhui white goose. IFN-γ, IL-1α and TNF-α might be synthesized by cerebellar cortex itself, and NGF-β could be transported from regions which project to Purkinje cells. IFN-γ may interfer the transfer of granular cells, and NGF-β may have neurotrophic functions that are beneficial to the growth and development of Purkinje cells

Ugi Multicomponent Reaction Product: The Inhibitive Effect on DNA Oxidation Depends upon the Isocyanide Moiety

The hydroxyl-substituted benzoic acid (as phenyl group A in the product), aniline (as phenyl group B in the product), benzaldehyde (as phenyl group C in the product), and four isocyanides are employed to synthesize bis-amide via an Ugi four-component reaction. The effects of the obtained 20 bis-amides on quenching radicals and inhibiting DNA oxidation are estimated. It is found that the antioxidant effectiveness of bis-amide generated by hydroxyl groups is markedly influenced by the structural feature derived from isocyanide. The phenolic hydroxyl group attaching to phenyl group A plays a major role in scavenging radicals, and the radical-scavenging property is reinforced by the structural moiety introduced from ferrocenylmethyl isocyanide. The same conclusion is also obtained when bis-amides are used to inhibit DNA oxidation. It is still found that the ferrocenylmethyl moiety enhances the antioxidant effect of hydroxyl group at phenyl group A in protecting DNA against the oxidation. Moreover, when the bis-amide is prepared by the same isocyanide, e.g. ethyl isocyanoacetate, it is found that the hydroxyl group at phenyl group C plays the major role in inhibiting DNA oxidation, followed by the hydroxyl groups attaching to phenyl groups B and A

Solvent-Free and Catalyst-Free Biginelli Reaction To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To Express Radical-Scavenging Ability

Benzoyl and ferrocenoyl 3,4-dihydropyrimidin-2­(1<i>H</i>)-ones (-thiones) (DHPMs) were synthesized in modest yields via catalyst-free and solvent-free Biginelli condensation of 1-phenylbutane-1,3-dione or 1-ferrocenylbutane-1,3-dione, hydroxyl benzaldehyde, and urea or thiourea. This synthetic protocol revealed that catalysts may not be necessary for the self-assembling Biginelli reaction. The radical-scavenging abilities of the obtained 11 DHPMs were carried out by reacting with 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS^+•), galvinoxyl radical, and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), respectively. The variation of the concentration of these radicals with the reaction time (<i>t</i>) followed exponential function, [radical] = <i>A<b>e</b></i>^{–<i>t</i>/<i>a</i>} + <i>B<b>e</b></i>^{–<i>t</i>/<i>b</i>} + <i>C</i>. Then, the differential style of this equation led to the relationship between the reaction rate (<i><b>r</b></i>) and the reaction time (<i>t</i>), –<i>d</i>[radical]/<i>dt</i> = (<i>A</i>/<i>a</i>)<i><b>e</b></i>^{–<i>t</i>/<i>a</i>} + (<i>B</i>/<i>b</i>)<i><b>e</b></i>^{–<i>t</i>/<i>b</i>}, which can be used to calculate the reaction rate at any time point. On the basis of the concept of the reaction rate, <i><b>r</b></i> = <i><b>k</b></i>[radical]­[antioxidant], the rate constant (<i><b>k</b></i>) can be calculated with the time point being <i>t</i> = 0. By the comparison of <i><b>k</b></i> of DHPMs, it can be concluded that phenolic <i>ortho</i>-dihydroxyl groups markedly enhanced the abilities of DHPMs to quench ABTS^+•, but the introduction of ferrocenoyl group made DHPMs efficient ABTS^+• scavengers even in the absence of phenolic hydroxyl group. This phenomenon was also found in DHPM-scavenging galvinoxyl radical. In contrast, the ferrocenoyl group cannot enhance the abilities of DHPMs to scavenge DPPH, and phenolic <i>ortho</i>-dihydroxyl groups still played the key role in this case

Coumarin-Fused Coumarin: Antioxidant Story from <i>N</i>,<i>N</i>‑Dimethylamino and Hydroxyl Groups

Two coumarin skeletons can form chromeno­[3,4-<i>c</i>]­chromene-6,7-dione by sharing with the CC in lactone. The aim of the present work was to explore the antioxidant effectiveness of the coumarin-fused coumarin via six synthetic compounds containing hydroxyl and <i>N</i>,<i>N</i>-dimethylamino as the functional groups. The abilities to quench 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS^+•), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical revealed that the rate constant for scavenging radicals was related to the amount of hydroxyl group in the scaffold of coumarin-fused coumarin. But coumarin-fused coumarin was able to inhibit DNA oxidations caused by ^•OH, Cu²⁺/glutathione (GSH), and 2,2′-azobis­(2-amidinopropane hydrochloride) (AAPH) even in the absence of hydroxyl group. In particular, a hydroxyl and an <i>N</i>,<i>N</i>-dimethylamino group locating at different benzene rings increased the inhibitory effect of coumarin-fused coumarin on AAPH-induced oxidation of DNA about 3 times higher than a single hydroxyl group, whereas <i>N</i>,<i>N</i>-dimethylamino-substituted coumarin-fused coumarin possessed high activity toward ^•OH-induced oxidation of DNA without the hydroxyl group contained. Therefore, the hydroxyl group together with <i>N</i>,<i>N</i>-dimethylamino group may be a novel combination for the design of coumarin-fused heterocyclic antioxidants

Coumestan Inhibits Radical-Induced Oxidation of DNA: Is Hydroxyl a Necessary Functional Group?

Coumestan is a natural tetracycle with a CC bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS^•+), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by ^•OH, Cu²⁺/glutathione (GSH), and 2,2′-azobis­(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit ^•OH-, Cu²⁺/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit ^•OH- and Cu²⁺/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant

Ferrocenyl-Appended Aurone and Flavone: Which Possesses Higher Inhibitory Effects on DNA Oxidation and Radicals?

The aim of the present work was to compare the antioxidative effect of the ferrocenyl-appended aurone with that of ferrocenyl-appended flavone; therefore, nine aurones together with the flavone-type analogues were synthesized by using chalcone as the reactant. The radical-scavenging property was evaluated by reacting with the 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS^<b>+·</b>), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. The cytotoxicity was estimated by inhibiting 2,2′-azobis­(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the introduction of the ferrocenyl group remarkably increased the radical-scavenging activities of aurone and flavone. Especially, the ferrocenyl group in flavones can quench radicals even in the absence of the phenolic hydroxyl group, while ferrocenyl-appended aurones can efficiently protect DNA against AAPH-induced oxidation. Therefore, the antioxidative effect was generated by the ferrocenyl group and enhanced by the electron-donating group attaching to the <i>para</i>-position of the ferrocenyl group. Introducing the ferrocenyl group into natural compounds may be a useful strategy for increasing the antioxidative effectiveness

The crystallization of active pharmaceutical ingredients with low melting points in the presence of liquid–liquid phase separation

10.3390/cryst11111326Crystals1111132