Category: Pyrazines

On August 13, 2020, Crawford, James J.; Lee, Wendy; Johnson, Adam R.; Delatorre, Kelly J.; Chen, Jacob; Eigenbrot, Charles; Heidmann, Julia; Kakiuchi-Kiyota, Satoko; Katewa, Arna; Kiefer, James R.; Liu, Lichuan; Lubach, Joseph W.; Misner, Dinah; Purkey, Hans; Reif, Karin; Vogt, Jennifer; Wong, Harvey; Yu, Christine; Young, Wendy B. published an article.Synthetic Route of 87486-34-8 The title of the article was Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity. And the article contained the following:

Bruton’s tyrosine kinase (Btk) is thought to play a pathogenic role in chronic immune diseases such as rheumatoid arthritis and lupus. While covalent, irreversible Btk inhibitors are approved for treatment of hematol. malignancies, they are not approved for autoimmune indications. In efforts to develop addnl. series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clin. stage inhibitor fenebrutinib using cyclopropyl amide isosteres of the 2-aminopyridyl group to occupy the flat, lipophilic H2 pocket. While drug-like properties were retained – and in some cases improved – a safety liability in the form of hERG inhibition was observed When a fluorocyclopropyl amide was incorporated, Btk and off-target activity was found to be stereodependent and a lead compound was identified in the form of the (R,R) stereoisomer. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Synthetic Route of 87486-34-8

The Article related to fluorocyclopropyl amide btk inhibitor stereochem herg inhibition, Alicyclic Compounds: Cyclopropanes and other aspects.Synthetic Route of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Fatoki, Toluwase Hezekiah; Ibraheem, Omodele; Ogunyemi, Ibukun Oladejo; Akinmoladun, Afolabi Clement; Ugboko, Harriet U.; Adeseko, Catherine Joke; Awofisayo, Oladoja A.; Olusegun, Sunday Joseph; Enibukun, Jesupemi Mercy published an article in 2021, the title of the article was Network analysis, sequence and structure dynamics of key proteins of coronavirus and human host, and molecular docking of selected phytochemicals of nine medicinal plants.Computed Properties of 55779-48-1 And the article contains the following content:

The novel coronavirus of 2019 (nCoV-19) has become a pandemic, affecting over 205 nations with over 7,410,000 confirmed cases which has resulted to over 418,000 deaths worldwide. This study aimed to identify potential therapeutic compounds and phytochems. of medicinal plants that have potential to modulate the expression network of genes that are involve in SARS-CoV-2 pathol. in human host and to understand the dynamics key proteins involved in the virus-host interactions. The method used include gene network anal., mol. docking, and sequence and structure dynamics simulations. The results identified DNA-dependent protein kinase (DNA-PK) and Protein kinase CK2 as key players in SARS-CoV-2 lifecycle. Among the predicted drugs compounds, clemizole, monorden, spironolactone and tanespimycin showed high binding energies; among the studied repurposing compounds, remdesivir, simeprevir and valinomycin showed high binding energies; among the predicted acidic compounds, acetylursolic acid and hardwickiic acid gave high binding energies; while among the studied anthraquinones and glycosides compounds, ellagitannin and friedelanone showed high binding energies against 3-Chymotrypsin-like protease (3CLpro), Papain-like protease (PLpro), helicase (nsp13), RNA-dependent RNA polymerase (nsp12), 2′-O-ribose methyltransferase (nsp16) of SARS-CoV-2 and DNA-PK and CK2alpha in human. The order of affinity for CoV proteins is 5Y3E > 6NUS > 6JYT > 2XYR > 3VB6. Finally, medicinal plants with phytochems. such as caffeine, ellagic acid, quercetin and their derivatives could possibly remediate COVID-19. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Computed Properties of 55779-48-1

The Article related to human covid19 virus mol docking dynamic simulation free energy, covid-19, sars-cov-2, drug discovery, gene expression network, molecular docking and dynamics simulation, Pharmacology: Structure-Activity and other aspects.Computed Properties of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On July 11, 2013, Jin, Meizhong; Petronella, Brenda A.; Cooke, Andy; Kadalbajoo, Mridula; Siu, Kam W.; Kleinberg, Andrew; May, Earl W.; Gokhale, Prafulla C.; Schulz, Ryan; Kahler, Jennifer; Bittner, Mark A.; Foreman, Kenneth; Pachter, Jonathan A.; Wild, Robert; Epstein, David; Mulvihill, Mark J. published an article.Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the article was Discovery of Novel Insulin-Like Growth Factor-1 Receptor Inhibitors with Unique Time-Dependent Binding Kinetics. And the article contained the following:

This letter describes a series of small mol. inhibitors of IGF-1R with unique time-dependent binding kinetics and slow off-rates. Structure-activity and structure-kinetic relationships were elucidated and guided further optimizations within the series, culminating in compound 2. With an IGF-1R dissociative half-life (t1/2) of >100 h, compound 2 demonstrated significant and extended PD effects in conjunction with tumor growth inhibition in xenograft models at a remarkably low and intermittent dose, which correlated with the observed in vitro slow off-rate properties. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to preparation igf1 receptor inhibitor binding kinetics structure, insulin-like growth factor-1 receptor (igf-1r), cancer, slow off-rate, time-dependent inhibition, Pharmacology: Structure-Activity and other aspects.Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On June 15, 2020, Weihs, Felix; Gel, Murat; Wang, Jian; Anderson, Alisha; Trowell, Stephen; Dacres, Helen published an article.COA of Formula: C26H21N3O3 The title of the article was Development and characterisation of a compact device for rapid real-time-on-chip detection of thrombin activity in human serum using bioluminescence resonance energy transfer (BRET). And the article contained the following:

Bioluminescence resonance energy transfer (BRET) is a sensitive optical detection method that can monitor changes in the relative orientation and the phys. proximity of mols. in real-time. Since the light is generated internally by a bioluminescent protein, BRET does not rely on an external light source. The use of BRET simultaneously simplifies the hardware required for sensing and offers improved detection limits and sensitivity for applications targeting point-of-care bio-sensing. In this paper, we report a compact micro reactor integrating a thermostat with a re-useable glass-chip comprising a chaotic mixer, an incubation channel and optical detection chamber. The device was optimized to detect thrombin activities in serum, achieving a thrombin detection limit of 38μU/μl in 10% (volume/volume) human serum in a 5 min assay time. This is a 90% assay time reduction, compared with previous BRET-based work or other technologies. The low cost associated with this approach, low interference from human serum and other proteases and good reproducibility (CV = 0.2-3.6%), establish new performance standards for point-of-care diagnostics with samples of human serum. Importantly, measuring protease activity levels, rather than concentrations, is the most informative approach for clin. diagnostics. Of the recently reported ultra-sensitive thrombin sensing techniques, this is the only one to measure thrombin activity in serum dilutions, rather than simply quantifying thrombin concentrations The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).COA of Formula: C26H21N3O3

The Article related to serum thrombin real timeon chip bioluminescence resonance energy transfer, blood analysis, lab-on-a-chip, microfluidics, optical sensor, protease activity, thrombin, Biochemical Methods: Biological and other aspects.COA of Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On November 5, 2021, Mizuno, Gaku; Yano, Daichi; Paitio, Jose; Endo, Hiromitsu; Oba, Yuichi published an article.Electric Literature of 55779-48-1 The title of the article was Etmopterus lantern sharks use coelenterazine as substrate for their luciferin-luciferase bioluminescence system. And the article contained the following:

The lantern shark genus Etmopterus contains approx. 40 species of deep-sea bioluminescent cartilaginous fishes. They emit blue light mainly from the ventral body surface. The biol. functions of this bioluminescence have been discussed based on the luminescence patterns, but the bioluminescence mechanism remains uncertain. In this study, we detected both coelenterazine and coelenterazine-dependent luciferase activity in the ventral photophore tissue of Etmopterus molleri. The results suggested that bioluminescence in lantern sharks is produced using coelenterazine as the substrate for the luciferin-luciferase reaction, as some luminous bony fishes. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Electric Literature of 55779-48-1

The Article related to coelenterazine luciferin luciferase bioluminescence etmopterus, bioluminescence, coelenterazine, etmopterus, lantern shark, luciferase, luciferin, Biochemical Methods: Biological and other aspects.Electric Literature of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On February 28, 2022, Larionova, Marina D.; Wu, Lijie; Eremeeva, Elena V.; Natashin, Pavel V.; Gulnov, Dmitry V.; Nemtseva, Elena V.; Liu, Dongsheng; Liu, Zhi-Jie; Vysotski, Eugene S. published an article.Application In Synthesis of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one The title of the article was Crystal structure of semisynthetic obelin-v. And the article contained the following:

Coelenterazine-v (CTZ-v), a synthetic derivative with an addnl. benzyl ring, yields a bright bioluminescence of Renilla luciferase and its “yellow” mutant with a significant shift in the emission spectrum toward longer wavelengths, which makes it the substrate of choice for deep tissue imaging. Although Ca2+-regulated photoproteins activated with CTZ-v also display red-shifted light emission, in contrast to Renilla luciferase their bioluminescence activities are very low, which makes photoproteins activated by CTZ-v unusable for calcium imaging. Here, we report the crystal structure of Ca2+-regulated photoprotein obelin with 2-hydroperoxycoelenterazine-v (obelin-v) at 1.80 S resolution The structures of obelin-v and obelin bound with native CTZ revealed almost no difference; only the minor rearrangement in hydrogen-bond pattern and slightly increased distances between key active site residues and some atoms of 2-hydroperoxycoelenterazine-v were found. The fluorescence quantum yield (ΦFL) of obelin bound with coelenteramide-v (0.24) turned out to be even higher than that of obelin with native coelenteramide (0.19). Since both obelins are in effect the enzyme-substrate complexes containing the 2-hydroperoxy adduct of CTZ-v or CTZ, we reasonably assume the chem. reaction mechanisms and the yields of the reaction products (ΦR) to be similar for both obelins. Based on these findings we suggest that low bioluminescence activity of obelin-v is caused by the low efficiency of generating an electronic excited state (ΦS). In turn, the low ΦS value as compared to that of native CTZ might be the result of small changes in the substrate microenvironment in the obelin-v active site. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Application In Synthesis of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

The Article related to obelin coelenterazine crystal structure, analog, bioluminescence, coelenterazine, coelenterazine-v, obelin, photoprotein, protein structure, Biochemical Methods: Biological and other aspects.Application In Synthesis of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On April 2, 2022, Bashmakova, Eugenia E.; Panamarev, Nikita S.; Kudryavtsev, Alexander N.; Frank, Ludmila A. published an article.COA of Formula: C26H21N3O3 The title of the article was N-extended photoprotein obelin to competitively detect small protein tumor markers. And the article contained the following:

Two variants of Ca2+-regulated photoprotein obelin, extended from the N-terminus with small tumor markers – melanoma inhibitory activity protein (MIA) and survivin, one of the protein inhibitors of apoptosis, were designed, obtained and studied. Both domains in the obtained hybrid proteins exhibit the properties of the initial mols.: the main features of Ca2+-triggered bioluminescence are close to those of obelin, and the tumor markers domains are recognized and bound by the corresponding antibodies. The obtained hybrids compete with the corresponding tumor markers for binding with antibodies, immobilized on the surface and their use has been shown to be promising as bioluminescent labels in a one-stage solid-phase competitive immunoassay. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).COA of Formula: C26H21N3O3

The Article related to photoprotein obelin protein tumor marker, competitive assay, genetic fusion, photoprotein obelin, tumor marker, Biochemical Methods: Biological and other aspects.COA of Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On February 28, 2019, Chen, Jie; Landegger, Lukas D.; Sun, Yao; Ren, Jun; Maimon, Nir; Wu, Limeng; Ng, Mei R.; Chen, John W.; Zhang, Na; Zhao, Yingchao; Gao, Xing; Fujita, Takeshi; Roberge, Sylvie; Huang, Peigen; Jain, Rakesh K.; Plotkin, Scott R.; Stankovic, Konstantina M.; Xu, Lei published an article.Electric Literature of 55779-48-1 The title of the article was A cerebellopontine angle mouse model for the investigation of tumor biology, hearing, and neurological function in NF2-related vestibular schwannoma. And the article contained the following:

Neurofibromatosis type II (NF2) is a disease that lacks effective therapies. NF2 is characterized by bilateral vestibular schwannomas (VSs) that cause progressive and debilitating hearing loss, leading to social isolation and increased rates of depression. A major limitation in NF2 basic and translational research is the lack of animal models that allow the full spectrum of research into the biol. and mol. mechanisms of NF2 tumor progression, as well as the effects on neurol. function. In this protocol, we describe how to inject schwannoma cells into the mouse brain cerebellopontine angle (CPA) region. We also describe how to apply state-of-the-art intravital imaging and hearing assessment techniques to study tumor growth and hearing loss. In addition, ataxia, angiogenesis, and tumor-stroma interaction assays can be applied, and the model can be used to test the efficacy of novel therapeutic approaches. By studying the disease from every angle, this model offers the potential to unravel the basic biol. underpinnings of NF2 and to develop novel therapeutics to control this devastating disease. Our protocol can be adapted to study other diseases within the CPA, including meningiomas, lipomas, vascular malformations, hemangiomas, epidermoid cysts, cerebellar astrocytomas, and metastatic lesions. The entire surgical procedure takes ∼45 min per mouse and allows for subsequent longitudinal imaging, as well as neurol. and hearing assessment, for up to 2 mo. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Electric Literature of 55779-48-1

The Article related to hearing neurofibromatosis 2 schwannoma cerebellopontine angle mouse model, Biochemical Methods: Biological and other aspects.Electric Literature of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On April 30, 2019, Kobayashi, Hiroyuki; Picard, Louis-Philippe; Schonegge, Anne-Marie; Bouvier, Michel published an article.Recommanded Product: 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one The title of the article was Bioluminescence resonance energy transfer-based imaging of protein-protein interactions in living cells. And the article contained the following:

Because BRET occurs when the distance between the donor and acceptor is <10 nm, and its efficiency is inversely proportional to the sixth power of distance, it has gained popularity as a proximity-based assay to monitor protein-protein interactions and conformational rearrangements in live cells. In such assays, one protein of interest is fused to a bioluminescent energy donor (luciferases from Renilla reniformis or Oplophorus gracilirostris), and the other protein is fused to a fluorescent energy acceptor (such as GFP or YFP). Because the BRET donor does not require an external light source, it does not lead to phototoxicity or autofluorescence. It therefore represents an interesting alternative to fluorescence-based imaging such as FRET. However, the low signal output of BRET energy donors has limited the spatiotemporal resolution of BRET imaging. Here, we describe how recent improvements in detection devices and BRET probes can be used to markedly improve the resolution of BRET imaging, thus widening the field of BRET imaging applications. The protocol described herein involves three main stages. First, cell preparation and transfection require 3 d, including cell culture time. Second, image acquisition takes 10-120 min per sample, after an initial 60 min for microscope setup. Finally, image anal. typically takes 1-2 h. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Recommanded Product: 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

The Article related to bioluminescence resonance energy transfer living cell protein interaction, Biochemical Methods: Biological and other aspects.Recommanded Product: 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 1, 2020, Ikeda, Yuma; Tanaka, Masanobu; Nishihara, Ryo; Hiruta, Yuki; Citterio, Daniel; Suzuki, Koji; Niwa, Kazuki published an article.Synthetic Route of 55779-48-1 The title of the article was Quantitative evaluation of luminescence intensity from enzymatic luminescence reaction of coelenterazine and analogues. And the article contained the following:

Recent advances in bioluminescence technol. rely on the discovery of luciferin-luciferase pairs having excellent luminescence activity. Here, we focus on coelenterazine (CTZ) and its analogs and quant. investigate reaction factors, including bioluminescence reaction quantum yield (φBL) and enzyme reaction kinetics (turnover rate, kcat), determining the luminescence intensity to design brighter reaction systems. Initially, it was confirmed that the CTZ was kept stable during the storage and the φBL value measuring experiment in terms of comparative study using benzyl-protected CTZ. Using a luminometer whose absolute responsivity is calibrated for each luminescence reaction spectrum, we absolutely measured φBL and other reaction factors of CTZ and 3 types of blue-shifted CTZ analogs, CTZ 400a, 6-pi-H-CTZ and 6-pi-Ph-CTZ. The results suggested that there was no significant difference in reaction kinetics, but a clear difference in φBL (up to 22-fold), which was presumably due to an improvement in fluorescence quantum yield (φFL) of the corresponding coelenteramide (CTMD), oxidized form of CTZ. Our evaluation suggests that the design of CTZ analogs considering φFL is important for developing a bright luminescent reaction system. The experimental process involved the reaction of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one(cas: 55779-48-1).Synthetic Route of 55779-48-1

The Article related to tert butoxycarbonyl coelenterazine bioluminescence spectrum charge coupled device, Placeholder for records without volume info and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem