153493-48-2Relevant articles and documents
5,6-Di(2-fluoro-2,2-dinitroethoxy)furazano[3,4-: B] pyrazine: A high performance melt-cast energetic material and its polycrystalline properties
Ma, Qing,Lu, Zhipeng,Liao, Longyu,Huang, Jinglun,Liu, Dabin,Li, Jinshan,Fan, Guijuan
, p. 38844 - 38852 (2017)
5,6-Di(2-fluoro-2,2-dinitroethoxy)furazano[3,4-b]pyrazine was synthesized in a three-step process starting from 3,4-diaminofurazan (DAF) including a significant nucleophilic substitution reaction under the catalytic effect of trisodium phosphate dodecahydrate. Characterization of this molecule indicates that it possesses a higher crystal density than that of 2,4,6-trinitrotoluene (TNT) at ambient temperature with acceptable melting-point and energetic properties approaching those of 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) but with a higher thermal stability and lower sensitivity towards impact and friction. To investigate its polycrystalline properties, differential scanning calorimetry (DSC), powder-X-ray-diffraction (PXRD) and ab initio calculation using the Viena Ab initio simulation package (VASP) were employed.
1,2,3-Triazolo[4,5,-e]furazano[3,4,-b]pyrazine 6-oxide-a fused heterocycle with a roving hydrogen forms a new class of insensitive energetic materials
Thottempudi, Venugopal,Yin, Ping,Zhang, Jiaheng,Parrish, Damon A.,Shreeve, Jean'ne M.
, p. 542 - 548 (2014)
The straightforward synthesis and energetic properties of a new class of energetic materials, 1,2,3-triazolo- [4,5-e]furazano[3,4-b]pyrazine 6-oxide and its energetic salts are described. They were characterized by IR and multinuclear NMR spectroscopy, elemental analysis, differential scanning calorimetry, and single-crystal X-ray diffraction are given. The X-ray structures show that in the title compound, the hydrogen atom is bonded to the nitrogen in the pyrazine ring; however, in the salts, the negative charge is associated with the triazole nitrogen. Heats of formation for all compounds were calculated with the G2 method and then combined with experimentally determined densities to obtain detonation pressures (P) and velocities (D) by using EXPLO5 program. These new materials exhibit good densities and thermal stabilities, high heats of formation, acceptable detonation properties, and are insensitive to impact.
Synthesis and properties of 1,2,4-triazolo-1,2,4-triazolofurazanopyrazines
Khisamutdinov, G. Kh.,Korolev, V. L.,Parkhomenko, T. N.,Sharonova, V. M.,Artem'eva, E. S.,et al.
, p. 1700 - 1702 (1993)
New methods for the synthesis of 1,2,4-triazolo-1,2,4-triazolofurazanopyrazines with functional substituents of various types are proposed and some properties of these compounds are studied. - Key words: 1,2,4-triazolo-1,2,4-triazolofurazanopyrazines; heterocyclization reactions; methods of synthesis.
Solid-phase versus solution synthesis of asymmetrically disubstituted furazano[3,4-b]pyrazines
Fernández,García-Ochoa,Huss,Mallo,Bueno,Micheli,Paio,Piga,Zarantonello
, p. 4741 - 4745 (2002)
Herein we describe a straightforward solid-phase synthesis directed towards the preparation of families of asymmetrically disubstituted furazano[3,4-b]pyrazines by stepwise displacement of the two chlorine atoms in 5,6-dichlorofurazano[3,4-b]pyrazine by nucleophiles. This synthesis has avoided selectivity problems found in solution chemistry.
6-Amino[1,2,5]oxadiazolo[3,4- b]pyrazin-5-ol Derivatives as Efficacious Mitochondrial Uncouplers in STAM Mouse Model of Nonalcoholic Steatohepatitis
Salamoun, Joseph M.,Garcia, Christopher J.,Hargett, Stefan R.,Murray, Jacob H.,Chen, Sing-Young,Beretta, Martina,Alexopoulos, Stephanie J.,Shah, Divya P.,Olzomer, Ellen M.,Tucker, Simon P.,Hoehn, Kyle L.,Santos, Webster L.
, p. 6203 - 6224 (2020/07/14)
Small molecule mitochondrial uncouplers have recently garnered great interest for their potential in treating nonalcoholic steatohepatitis (NASH). In this study, we report the structure-activity relationship profiling of a 6-amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol core, which utilizes the hydroxy moiety as the proton transporter across the mitochondrial inner membrane. We demonstrate that a wide array of substituents is tolerated with this novel scaffold that increased cellular metabolic rates in vitro using changes in oxygen consumption rate as a readout. In particular, compound SHS4121705 (12i) displayed an EC50 of 4.3 μM in L6 myoblast cells and excellent oral bioavailability and liver exposure in mice. In the STAM mouse model of NASH, administration of 12i at 25 mg kg-1 day-1 lowered liver triglyceride levels and improved liver markers such as alanine aminotransferase, NAFLD activity score, and fibrosis. Importantly, no changes in body temperature or food intake were observed. As potential treatment of NASH, mitochondrial uncouplers show promise for future development.
Oxadiazolo[3,4- b]pyrazine-5,6-diamine Derivatives as Mitochondrial Uncouplers for the Potential Treatment of Nonalcoholic Steatohepatitis
Childress, Elizabeth S.,Salamoun, Joseph M.,Hargett, Stefan R.,Alexopoulos, Stephanie J.,Chen, Sing-Young,Shah, Divya P.,Santiago-Rivera, José,Garcia, Christopher J.,Dai, Yumin,Tucker, Simon P.,Hoehn, Kyle L.,Santos, Webster L.
, p. 2511 - 2526 (2020/03/10)
Small molecule mitochondrial uncouplers are emerging as a new class of molecules for the treatment of nonalcoholic steatohepatitis. We utilized BAM15, a potent protonophore that uncouples the mitochondria without depolarizing the plasma membrane, as a lead compound for structure-activity profiling. Using oxygen consumption rate as an assay for determining uncoupling activity, changes on the 5- and 6-position of the oxadiazolopyrazine core were introduced. Our studies suggest that unsymmetrical aniline derivatives bearing electron withdrawing groups are preferred compared to the symmetrical counterparts. In addition, alkyl substituents are not tolerated, and the N-H proton of the aniline ring is responsible for the protonophore activity. In particular, compound 10b had an EC50 value of 190 nM in L6 myoblast cells. In an in vivo model of NASH, 10b decreased liver triglyceride levels and showed improvement in fibrosis, inflammation, and plasma ALT. Taken together, our studies indicate that mitochondrial uncouplers have potential for the treatment of NASH.
COMPOSITIONS AND METHODS FOR PREPARING AND USING MITOCHONDRIAL UNCOUPLERS
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Paragraph 0161, (2018/12/13)
This disclosure provides compounds of Formula I, II, and III and pharmaceutically acceptable salts thereof for use as mitochondrial uncouplers, where the variables, e.g. R1-R9, (I) (II) (III) X1, X2, and Y1
Difurazan piperazine nitramines high-energy ionic salts and synthetic method thereof
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Paragraph 0033; 0034, (2018/03/24)
The invention discloses a synthetic method of difurazan piperazine nitramines high-energy ionic salts. The synthetic method comprises the following steps: carrying out amination on difurazan piperazine by using an amination reagent NH2OSO3Hto obtain diamino substituted DFP; carrying out nitrate amination reaction by nitro-sulfuric acid to obtain a nitramine intermediate; directly reacting the nitramine intermediate with various organic alkalis without separation due to high sensibility and unstability of the nitramine intermediate to obtain various difurazan piperazine nitramines high-energy ionic salts. The invention further provides a specific structure and performance of the difurazan piperazine nitramines high-energy ionic salt. The several brand-new difurazan piperazine nitramines high-energy ionic salts are obtained, and the range of a DFP-based energetic material is opened up.
Oxadiazolopyrazine derivatives as pharmaceutically active compounds
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Page/Page column 19; 25, (2010/02/11)
The present invention relates to furazanopyrazine derivatives of the general formula (I): wherein:R' represents -NR1R2 or -OR9R" represents -NR5-NR3R4, -NR5-ORb, -O-NR
Chemistry of furazano[3,4-b]pyrazines 3. Method for the synthesis of 5,6-disubstituted furazano[3,4-b]pyrazines
Starchenkov,Andrianov
, p. 1219 - 1233 (2007/10/03)
A method was developed for the synthesis of 5,6-dichlorofurazano[3,4-b]pyrazine (a compound with easily removed leaving groups). The optimum conditions for their substitution by various nucleophiles were determined. 1998 Plenum Publishing Corporation.
