16298-03-6Relevant articles and documents
A practical and step-economic route to Favipiravir
Liu, Feng-Liang,Li, Cui-Qin,Xiang, Hao-Yue,Feng, Si
, p. 2153 - 2158 (2017)
A practical and step-economic route to Favipiravir, an antiviral drug, was developed. Favipiravir was synthesized in only six steps from 3-aminopyrazine-2-carboxylic acid with an overall yield of about 22.3%. Key intermediates 3 and 6 were obtained in excellent purity via recrystallization from optimized solvents, which was beneficial to large-scale production. In the key synthetic reaction, 3,6-dichloropyrazine-2-carbonitrile (6) was reacted sequentially, in one pot, with KF and 30% H2O2 to give (after crystallization from 95% EtOH) favipiravir as colorless crystals, with a 60% yield for this final step of the synthesis.
Application of the Curtius rearrangement in a convenient preparation of 3-amino-pyrazinecarboxylic acid, methyl ester
Chen,Hinkley,Wise,Townsend
, p. 617 - 622 (1996)
An efficient and convenient synthesis of 3-aminopyrazinecarboxylic acid, methyl ester (7) has been achieved through the use of a Curtius rearrangement.
Derivatives of 3-Aminopyrazine-2-carboxamides: Synthesis, antimicrobial evaluation, and in vitro cytotoxicity
Bouz, Ghada,Semelková, Lucia,Jand’ourek, Ond?ej,Kone?ná, Klára,Paterová, Pavla,Navrátilová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Dole?al, Martin,Zitko, Jan
, (2019/04/05)
We report the design, synthesis, and in vitro antimicrobial activity of a series of N-substituted 3-aminopyrazine-2-carboxamides with free amino groups in position 3 on the pyrazine ring. Based on various substituents on the carboxamidic moiety, the series is subdivided into benzyl, alkyl, and phenyl derivatives. The three-dimensional structures of the title compounds were predicted using energy minimization and low mode molecular dynamics under AMBER10:EHT forcefield. Compounds were evaluated for antimycobacterial, antibacterial, and antifungal activities in vitro. The most active compound against Mycobacterium tuberculosis H37Rv (Mtb) was 3-amino-N-(2,4-dimethoxyphenyl)pyrazine-2-carboxamide (17, MIC = 12.5 μg/mL, 46 μM). Antimycobacterial activity against Mtb and M. kansasii along with antibacterial activity increased among the alkyl derivatives with increasing the length of carbon side chain. Antibacterial activity was observed for phenyl and alkyl derivatives, but not for benzyl derivatives. Antifungal activity was observed in all structural subtypes, mainly against Trichophyton interdigitale and Candida albicans. The four most active compounds (compounds 10, 16, 17, 20) were evaluated for their in vitro cytotoxicity in HepG2 cancer cell line; only compound 20 was found to exert some level of cytotoxicity. Compounds belonging to the current series were compared to previously published, structurally related compounds in terms of antimicrobial activity to draw structure activity relationships conclusions.
Discovering a new class of antifungal agents that selectively inhibits microbial carbonic anhydrases
Annunziato, Giannamaria,Giovati, Laura,Angeli, Andrea,Pavone, Marialaura,Del Prete, Sonia,Pieroni, Marco,Capasso, Clemente,Bruno, Agostino,Conti, Stefania,Magliani, Walter,Supuran, Claudiu T.,Costantino, Gabriele
, p. 1537 - 1544 (2018/10/15)
Infections caused by pathogens resistant to the available antimicrobial treatments represent nowadays a threat to global public health. Recently, it has been demonstrated that carbonic anhydrases (CAs) are essential for the growth of many pathogens and their inhibition leads to growth defects. Principal drawbacks in using CA inhibitors (CAIs) as antimicrobial agents are the side effects due to the lack of selectivity toward human CA isoforms. Herein we report a new class of CAIs, which preferentially interacts with microbial CA active sites over the human ones. The mechanism of action of these inhibitors was investigated against an important fungal pathogen, Cryptococcus neoformans, revealing that they are also able to inhibit CA in microbial cells growing in vitro. At our best knowledge, this is the first report on newly designed synthetic compounds selectively targeting β-CAs and provides a proof of concept of microbial CAs suitability as an antimicrobial drug target.
Method for synthesis of favipiravir
-
Paragraph 0137; 0138; 0139; 0140, (2017/07/19)
The invention discloses a method for synthesis of favipiravir. The method comprises an esterification reaction of 3-aminopyrazine-2-carboxylic acid and an alcohol, a bromination reaction, a diazotization reaction, an ammonolysis reaction, a chlorination-dehydration reaction, a one-pot series connection aromatic ring fluorination reaction, a cyan-hydrolysis reaction, an aromatic ring hydroxyl substitution reaction, and purification treatment so that favipiravir is obtained. The method utilizes 3-amino-2-carboxypyrazine as a raw material to synthesize favipiravir through 8-step reactions and has a total yield of 26%. The key intermediates 3 and 6 in the method are purified by recrystallization so that column chromatography separation in the literature is avoided. The final three reactions are finished by a one-pot method so that the operation is simplified. The synthesis method improves a yield, realizes a low cost and green economy and is conducive to industrial production.
Aminopyrazine Pathway to the Moco Metabolite Dephospho Form A
Klewe, Anne,Kruse, Tobias,Lindel, Thomas
, p. 11230 - 11233 (2017/08/26)
An efficient synthesis of the molybdopterin/molybdenum cofactor (Moco) oxidation product dephospho Form A is described that assembles the pteridinone system starting from an iodinated aminopyrazine. The sodium salt of dephospho Form A could be purified by precipitation from methanol, which paved the way to the title compound in the 100 mg range. By HPLC, the synthetic material was compared with a sample isolated from a recombinant Moco containing protein. Analysis of dephospho Form A is the only method that allows the quantification of the Moco content of crude cell extracts and recombinant protein preparations.
Preparation method for pyrazine derivative
-
Paragraph 0021; 0022, (2018/03/24)
The invention discloses a preparation method for a pyrazine derivative 3-amino-6-(3-chloro-5-methylphenyl)pyrazine-2-carboxamide. The method comprises the following steps: 3-aminopyrazine-2-carboxylic acid is used as a starting raw material, an esterification reaction is performed, an amidation reaction is performed, a bromination reaction is performed, a coupling reaction is performed, and therefore the objective product is obtained. The compound is an important pharmaceutical intermediate.
Azaindole synthesis through dual activation catalysis with N-heterocyclic carbenes
Sharma, Hayden A.,Todd Hovey,Scheidt, Karl A.
supporting information, p. 9283 - 9286 (2016/07/25)
A convergent, transition-metal-free synthesis of 2-aryl-azaindoles has been developed. The interception of a reactive aza-ortho-azaquinone methide intermediate by an acyl anion equivalent generated through carbene catalysis provides high yields, a wide substrate scope, and the synthesis of previously inaccessible azaindoles.
Pyrazine-based Syk kinase inhibitors
Forns, Pilar,Esteve, Cristina,Taboada, Lorena,Alonso, Juan Antonio,Orellana, Adelina,Maldonado, Mónica,Carre?o, Cristina,Ramis, Isabel,López, Manel,Miralpeix, Montserrat,Vidal, Bernat
scheme or table, p. 2784 - 2788 (2012/05/20)
A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.
Synthesis of N-substituted-6-alkoxypteridin-4-amine
Duan, Chonggang,Jia, Jiong,Zhu, Rongxiu,Wang, Jianwu
, p. 865 - 872 (2012/10/29)
A novel seven-step methodology for the synthesis of N-substituted-6- alkoxypteridin-4-amine has been developed with the total yields of 35.4-41%. Twenty new compounds were synthesized by heterocyclization of easily prepared 3-amino-6-bromopyrazine-2-carboxamide, subsequent alkoxylation, chlorination, and nucleophilic substitution. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS, and elemental analysis. The structure of N-(3-chloro-4-fluorophenyl)-6-ethoxypteridin-4-amine was further determined by X-ray crystallographic analysis. It was found that different chlorinating reagents gave different products. The possible chlorination mechanism was discussed.
