6966-01-4Relevant academic research and scientific papers
First synthesis of piperazine-derived [1,2,4]triazolo[1,5-a]pyrazine as an adenosine A2a receptor antagonist
Peng, Hairuo,Sha, Li,Chang, He Xi,Vessels, Jeffery T.,Haque, Serajul,Conlon, Patrick R.,Dowling, James E.,Wang, Joy,Engber, Thomas M.,Kumaravel, Gnanasambandam,Scott, Daniel M.,Petter, Russell C.
, p. 2321 - 2327 (2005)
Synthesis of piperazine-derived 2-furan-2-yl-[1,2,4]triazolo[1,5-a] pyrazines was achieved using methyl 3-amino-2-pyrazinecarboxylate. Introduction of the piperazine to the pyrazine template was achieved through a pteridin-4-one intermediate (7). Cyclization of the [1,2,4]triazolo[1,5-a]pyrazine ring was accomplished by amination of pyrazine (8) followed by condensation with 2-furaldehyde. Curtius rearrangement installed the amine to afford template (11). As one example of derivatizing 11, 6N-(4-(2,4,6-trifluorobenzyl)piperazin-1-yl)-2-(furan-2-yl)-[1,2,4]triazolo-[1,5-a]pyrazin-8-amine (12) showed moderate adenosine A2a receptor binding affinity and selectivity over the A1 receptor.{A figure is presented}.
Method for synthesis of favipiravir
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Paragraph 0141; 0142; 0143; 0167; 0168; 0169, (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.
A practical and step-economic route to Favipiravir
Liu, Feng-Liang,Li, Cui-Qin,Xiang, Hao-Yue,Feng, Si
, p. 2153 - 2158 (2017/09/30)
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.
A french pulls Wei synthetic method
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Paragraph 0041; 0042; 0043; 0044; 0045, (2017/08/25)
The invention belongs to the field of medicinal chemistry and particularly relates to a new synthesis method of Favipiravir. The method comprises the following steps: carrying out carboxyl protection on raw material shown in the formula (II) to generate a compound (III); carrying out diazotization hydrolysis reaction in the presence of concentrated sulfuric acid and sodium nitriteto generate a compound (IV); carrying out benzyl protection reaction to generate a compound (V), and then generating a compound (VI) in the presence of potassium fluoride and tetrabutylammonium bromide; removing a benzyl protection group to generate a compound (VII); and then adding an aminating agent to carry out amination to generate Favipiravir shown in the formula I. The method disclosed by the invention has the advantages that the reaction cycle is short, the operation is simple, the production cost is low, and the product is high in quality; therefore, the method is suitable for industrial production.
BCR-ABL kinase inhibitor and its application (by machine translation)
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Paragraph 0067, (2017/03/28)
The present invention relates to the field of chemical medicines, in particular to compounds as represented by formula I having BCR-ABL kinase inhibitory activity, or pharmaceutically acceptable salt, isomer, solvate, crystal or prodrug thereof, and pharmaceutical composition containing the compounds, and application of the compounds or compositions in drug preparation. The compounds of the present invention have strong inhibitory effect on BCR-ABL kinase, and can be used to treat diseases such as tumors.
SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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Page/Page column 66-67, (2015/01/16)
The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. (I)
SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR TREATMENT OF VIRAL DISEASES
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Page/Page column 70, (2015/01/16)
Disclosed are compounds of formula (I) that are useful as hepatitis C virus (HCV) NSSB polymerise inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NSSB polymerise activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
Aminopyrazinamides: Novel and specific GyrB inhibitors that kill replicating and nonreplicating mycobacterium tuberculosis
Shirude, Pravin S.,Madhavapeddi, Prashanti,Tucker, Julie A.,Murugan, Kannan,Patil, Vikas,Basavarajappa, Halesha,Raichurkar, Anandkumar V.,Humnabadkar, Vaishali,Hussein, Syeed,Sharma, Sreevalli,Ramya,Narayan, Chandan B.,Balganesh, Tanjore S.,Sambandamurthy, Vasan K.
, p. 519 - 523 (2013/05/08)
Aminopyrazinamides originated from a high throughput screen targeting the Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical tractability, robust structure-activity relationship, and potent antitubercular activity. The crystal structure of Msm GyrB in complex with one of the aminopyrazinamides revealed promising attributes of specificity against other broad spectrum pathogens and selectivity against eukaryotic kinases due to novel interactions at hydrophobic pocket, unlike other known GyrB inhibitors. The aminopyrazinamides display excellent mycobacterial kill under in vitro, intracellular, and hypoxic conditions.
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.
Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis
Andrews, Martin J.I.,Andrew Clase,Bar, Gregory,Tricarico, Giovanni,Edwards, Paul J.,Brys, Reginald,Chambers, Mark,Schmidt, Wolfgang,MacLeod, Angus,Hirst, Kim,Allen, Vivienne,Birault, Veronique,Le, Joelle,Harris, John,Self, Andrew,Nash, Kevin,Dixon, Graham
scheme or table, p. 2266 - 2270 (2012/05/04)
MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds.
