4744-50-7Relevant academic research and scientific papers
Design, synthesis, antimycobacterial evaluation, and in silico studies of 3-(phenylcarbamoyl)-pyrazine-2-carboxylic acids
Semelková, Lucia,Jano?cová, Petra,Fernandes, Carlos,Bouz, Ghada,Jand’Ourek, Ond?ej,Kone?ná, Klára,Paterová, Pavla,Navrátilová, Lucie,Kune?, Ji?í,Dole?al, Martin,Zitko, Jan
, (2017/09/25)
Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl)pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl)carbamoyl]pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 μg·mL?1 (5 μM). Propyl 3-{[4-(trifluoromethyl)phenyl]carbamoyl}pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 μg·mL?1. In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-β-D-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding.
Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus
Saudi, Milind,Zmurko, Joanna,Kaptein, Suzanne,Rozenski, Jef,Gadakh, Bharat,Chaltin, Patrick,Marchand, Arnaud,Neyts, Johan,Van Aerschot, Arthur
, p. 158 - 168 (2016/06/09)
High-Throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 1/4M), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 1/4M) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 1/4M and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 1/4M, with compound 6n being the most potent for this series with an EC50 0.4 1/4M and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity.
Synthesis and evaluation of imidazole-4,5-and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus
Saudi, Milind,Zmurko, Joanna,Kaptein, Suzanne,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
, p. 529 - 539 (2015/01/09)
The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b was observed to display the highest antiviral potency against YFV with an EC50 Combining double low line 1.85 μM. In addition, compounds 20a and 20b both potently inhibited replication of DENV (EC50 Combining double low line 0.93 μM) in Vero cells.
Process for the preparation of eszopiclone
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Page/Page column 4-5, (2008/12/06)
The invention relates to a process for making of 6-(5-chloro-2-pyridinyl)-6,7-dihydro-7-oxo-5H-pyrrolo-[3,4-b] pyrazin-5-yl-4-methyl piperazine-1-carboxylate, also known as zopiclone. The invention further describes an effective method for resolving of zopiclone into its enantiomers (eszopiclone and (R)-zopiclone) and also provides a method of recycling of (R)-zopiclone.
Hetero-annulated indazoles
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, (2008/06/13)
This invention is directed to heteroannulated indazoles namely to 2,5-disubstituted quinolino-, isoquinolino-, phthalazino-, and quinoxalino- annulated indazole-6(2H)-ones and related mono N-oxides. These compounds have been shown to have antitumor activity.
Application of the Curtius rearrangement in a convenient preparation of 3-amino-pyrazinecarboxylic acid, methyl ester
Chen,Hinkley,Wise,Townsend
, p. 617 - 622 (2007/10/03)
An efficient and convenient synthesis of 3-aminopyrazinecarboxylic acid, methyl ester (7) has been achieved through the use of a Curtius rearrangement.
The synthesis of 6,9-bis[(aminoalkyl)amino] substituted benzo[g]quinoxaline-, benzo[g]quinazoline- and benzo[g]phthalazine-5,10- diones via regiospecific displacements
Krapcho,Maresch,Helgason,Rosner,Hacker,Spinelli,Menta,Oliva
, p. 1597 - 1606 (2007/10/02)
The synthesis of 6,9-difluoro substituted benzo[g]quinoxaline-5,10-diones (3A), benzo[g]quinazoline-5,10-diones (3B) and benzo[g]phthalazine-5,10- diones (3C) have been accomplished. Treatment of 3A, 3B or 3C with diamines or N-(t-butoxycarbonyl)ethylenediamine led to the corresponding 6,9- bis[(aminoalkyl)amino]-substituted analogues related to 2A, 2B and 2C, respectively. The mono-substituted derivatives 4h and 4i could be isolated from displacements commencing from 3A. A competitive ring-opening of the pyrimidine ring of 2C occurred during the reaction with N,N- dimethylethylenediamine. Removal of the BOC-protecting group from 2Ac led to the hydrochloride salt 2Ab. A novel synthetic pathway to 6,9- dihydroxybenzo[g]phthalazine-5,10-dione (21a) was developed. Conversion of 21a to the ditosylate 21b was readily accomplished. Treatment of 21b with N,N-dimethylethylenediamine or N-(t-butoxycarbonyl)ethylenediamine led to 2Ca and 2Cc, respectively. Removal of the BOC-protecting group from 2Cc with trifluoroacetic acid followed by ion-exchange led to the hydrochloride salt 2Cb. Treatment of ditosylate 21b with N-(t-butoxycarbonyl)ethylenediamine also led to the mono-substituted analogue 25a along with a small amount of the O-S cleavage product 25b. Treatment of 25a with N,N- dimethylethylenediamine led to the unsymmetrically substituted derivative 25c which was converted into the trifluoroacetate salt 25d.
