- Identification of the C-Glycoside Synthases during Biosynthesis of the Pyrazole-C-Nucleosides Formycin and Pyrazofurin
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C-Nucleosides are characterized by a C?C rather than a C?N linkage between the heterocyclic base and the ribofuranose ring. While the biosynthesis of pseudouridine-C-nucleosides has been studied, less is known about the pyrazole-C-nucleosides such as the formycins and pyrazofurin. Herein, genome screening of Streptomyces candidus NRRL 3601 led to the discovery of the pyrazofurin biosynthetic gene cluster pyf. In vitro characterization of gene product PyfQ demonstrated that it is able to catalyze formation of the C-glycoside carboxyhydroxypyrazole ribonucleotide (CHPR) from 4-hydroxy-1H-pyrazole-3,5-dicarboxylic acid and phosphoribosyl pyrophosphate (PRPP). Similarly, ForT, the PyfQ homologue in the formycin pathway, can catalyze the coupling of 4-amino-1H-pyrazole-3,5-dicarboxylic acid and PRPP to form carboxyaminopyrazole ribonucleotide. Finally, PyfP and PyfT are shown to catalyze amidation of CHPR to pyrazofurin 5′-phosphate thereby establishing the latter stages of both pyrazofurin and formycin biosynthesis.
- Ren, Daan,Wang, Shao-An,Ko, Yeonjin,Geng, Yujie,Ogasawara, Yasushi,Liu, Hung-wen
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supporting information
p. 16512 - 16516
(2019/11/11)
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- PYRAZOLOPYRAZINES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE
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The present invention relates to a compound having the general formula (IIa) or (IIb), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph,codrug, cocrystal,prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
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Page/Page column 42
(2017/04/11)
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- Effect of configuration of 2-vinyldiazocarbonyl compounds on their reactivity: Experimental and computational study
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Non-fluorinated vinyldiazo compounds with trans-configuration irrespective of the nature of 3-R1-substituent (R1 = H, Me, TBSO) even under ambient conditions easily cyclize to produce pyrazoles, while cis-stereoisomers undergo similar ring closure only at elevated temperatures or decompose to produce vinyloxocarbene reaction products. The 3-CF 3-substituted analogues with cis- or trans-configuration do not produce pyrazoles at all, but on heating furnish only vinylcarbene derived products. DFT calculations of theoretical energy barriers adequately explain the different experimental reactivity found for stereoisomeric vinyldiazocarbonyl compounds, and a new model for their interconversion through the corresponding pyrazoles has been suggested. The Royal Society of Chemistry.
- Supurgibekov, Murat B.,Cantillo, David,Kappe, C. Oliver,Surya Prakash,Nikolaev, Valerij A.
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p. 682 - 689
(2014/01/06)
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- A novel series of glucagon receptor antagonists with reduced molecular weight and lipophilicity
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A novel series of glucagon receptor antagonists has been discovered. These pyrazole ethers and aminopyrazoles have lower molecular weight and increased polarity such that the molecules fall into better drug-like property space. This work has culminated in
- Filipski, Kevin J.,Bian, Jianwei,Ebner, David C.,Lee, Esther C.Y.,Li, Jian-Cheng,Sammons, Matthew F.,Wright, Stephen W.,Stevens, Benjamin D.,Didiuk, Mary T.,Tu, Meihua,Perreault, Christian,Brown, Janice,Atkinson, Karen,Tan, Beijing,Salatto, Christopher T.,Litchfield, John,Pfefferkorn, Jeffrey A.,Guzman-Perez, Angel
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scheme or table
p. 415 - 420
(2012/02/16)
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