Solution-phase Synthesis of a Combinatorial Library of 3-[4- (Coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid

Abstract: The parallel solution-phase synthesis of a new combinatorial library of 3-[4-(R1-coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides 9 has been developed. The synthesis involves two steps: 1) the synthesis of core building blocks – 3-[4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acids, 6 – by the reaction of 3-(ω-bromacetyl)coumarins 1 with 3-amino(thioxo)methylcarbamoylpropanoic acid (5); 2) the synthesis of the corresponding 3-[4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acids amides 9 using 1,1’-carbonyldimidazole as a coupling reagent. The advantages of the method compared to existing ones are discussed

Synthesis and Antimicrobial Activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones

The aim of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity.Materials and methods. 1Н NMR spectra were recorded on Varian Mercury-200 (200 MHz), 13C NMR spectra were acquired on Bruker Avance 500 1H NMR (500 MHz) and 13C NMR (125 MHz) in DMSO-d6 and CDCl3. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina.Results and discussion. The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. сoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase.Conclusions. Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress condition

Synthesis and Antimicrobial Activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones

The aim of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity.Materials and methods. 1Н NMR spectra were recorded on Varian Mercury-200 (200 MHz), 13C NMR spectra were acquired on Bruker Avance 500 1H NMR (500 MHz) and 13C NMR (125 MHz) in DMSO-d6 and CDCl3. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina.Results and discussion. The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. сoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase.Conclusions. Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress condition

Дослідження властивостей ресурсозберігаючої хромвмісної брикетованої легуючої добавки із рудної сировини

It was determined that the original oxide chromium-containing ore raw material is represented by granules of rounded shape the size of 250–600 µm. Along with Cr and Fe, it revealed Mg, Al, Si, Ca, and Ti. They probably were included in the composition of oxide ore impurities and can exert an indirect influence on the reducing processes. Phase composition of the briquetted raw material after the carbon thermal treatment consisted mainly of Cr2O3 and metal Cr with the presence of carbides Cr7C3 and Cr2C3. Diffraction maxima of metal Fe and its compounds had no explicit manifestation, indicating the presence of Fe as substitution atoms in the chromium-containing phases and compounds. The structure is heterogeneous.The content of residual oxygen confirms the presence, along with metal Cr, under-reduced oxide or oxy-carbide compounds. The residual oxygen could also be contained in the composition of oxide related ore impurities. This is confirmed by detection of the specified elements in the examined areas in the images of the microstructure. Excessive carbon content ensures the post-reduction of residual oxide component in a liquid metal in the process of alloying and enables protection against secondary oxidation of chromiumИсследованы фазовый состав, микроструктура хромсодержащего оксидного рудного сырья и соответствующих продуктов углеродотермического восстановления. Опытно-промышленным путем получен ресурсосберегающий хромсодержащий брикетированный легирующий материал с качественно новыми свойствами. Выявлена неоднородная оксикарбидная структура с избыточным содержанием углерода, что обеспечивает довосстановление остаточной оксидной составляющей при легировании и защиту от вторичного окисления хромаДосліджено фазовий склад, мікроструктуру хромвмісної оксидної рудної сировини і відповідних продуктів вуглецевотермічного відновлення. Дослідно-промисловим шляхом отримано ресурсозберігаючий хромвмісний брикетований легуючий матеріал з якісно новими властивостями. Виявлено неоднорідну оксикарбідну структуру з надлишковим вмістом вуглецю, що забезпечує довідновлення залишкової оксидної складової при легуванні та захист від вторинного окислення хром

Study Into Properties of the Resource­saving Chromium­containing Briquetted Alloying Additive From Ore Raw Materials

It was determined that the original oxide chromium-containing ore raw material is represented by granules of rounded shape the size of 250–600 µm. Along with Cr and Fe, it revealed Mg, Al, Si, Ca, and Ti. They probably were included in the composition of oxide ore impurities and can exert an indirect influence on the reducing processes. Phase composition of the briquetted raw material after the carbon thermal treatment consisted mainly of Cr2O3 and metal Cr with the presence of carbides Cr7C3 and Cr2C3. Diffraction maxima of metal Fe and its compounds had no explicit manifestation, indicating the presence of Fe as substitution atoms in the chromium-containing phases and compounds. The structure is heterogeneous.The content of residual oxygen confirms the presence, along with metal Cr, under-reduced oxide or oxy-carbide compounds. The residual oxygen could also be contained in the composition of oxide related ore impurities. This is confirmed by detection of the specified elements in the examined areas in the images of the microstructure. Excessive carbon content ensures the post-reduction of residual oxide component in a liquid metal in the process of alloying and enables protection against secondary oxidation of chromiu