Month: October 2022

On November 10, 2011, Barbosa, Antonio J. M.; Blomgren, Peter A.; Currie, Kevin S.; Krishnamoorthy, Ravi; Kropf, Jeffrey E.; Lee, Seung H.; Mitchell, Scott A.; Ortwine, Daniel; Schmitt, Aaron C.; Wang, Xiaojing; Xu, Jianjun; Young, Wendy; Zhang, Honglu; Zhao, Zhongdong; Zhichkin, Pavel E. published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of pyridone and azapyridone compounds as Btk inhibitors for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. And the patent contained the following:

The invention is related to the preparation of pyridones and azapyridones I [R1 = H, D, F, CN, OH, etc.; R2-4 = independently alkyl, Cl, NH2, OEt, etc.; R5 = (un)substituted (hetero)aryl, carbocyclyl, etc.; X = (S)0-2, N, NR6, O, CH and derivatives; R6 = H, F, NH2, OH, (un)substituted alkyl; Y, Y’ = independently CR6, N; Z1-4 = independently C, CH and derivatives, N; Z5 = CO, CH2 and derivatives, CH:N and derivatives, NH and derivatives, etc.; one of Z1 and Z2 or X and Z1, where X is not (S)0-2, forms a 5-7 membered aryl, carbocyclyl, heterocyclyl, heteroaryl ring; where alkyl, aryl, carbocyclyl, heterocyclyl, heteroaryl are optionally substituted] their stereoisomers, tautomers, and pharmaceutically acceptable salts useful for inhibiting Btk kinase, and for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. Methods of using I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathol. conditions, are disclosed. Thus, a multi-step synthesis starting from 5-nitropyrazole-3-carboxylic acid via cyclization of 1-(2-Bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole to 5-Methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine and cyclization of Et 1-(2-Aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate to 3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one was given for II. II inhibited Btk kinase (IC50 = 0.002 μM). The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

The Article related to pyridone azapyridone preparation btk inhibitor immune disease inflamation cancer, benzothienopyridinone pyrazinoindolone pyrazinobenzimidazolone methanopyrazinoindolone preparation rheumatoid arthritis and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 28, 2015, Laurent, Alain; Rose, Yannick published a patent.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the patent was Preparation of 8-aminoimidazo[3,4-a]pyrazine as Btk protein kinase inhibitors. And the patent contained the following:

The present invention relates to a novel family of protein kinase inhibitors, more specifically the present invention is directed to inhibitors of the members of the Tec and Src protein kinase families. The present invention also relates to processes for the preparation of these compounds [I; X = CH or N; R = H or each (un)substituted alkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; W = OCH2R11 or CH2OR11; R1 = each (un)substituted aryl or heteroaryl; X1, X2 = H or halogen; m, m1 = an integer from O to 4] or pharmaceutically acceptable salts, solvates, solvates of salts, stereoisomers, tautomers, isotopes, prodrugs, complexes or biol. active metabolites thereof, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative, inflammatory, inflammatory and autoimmune diseases, disorders or conditions in which protein kinase activity is implicated. Thus, a solution of intermediate (II) (300 mg), intermediate (III) (397 mg), N,N-dimethylglycine (231 mg), cesium carbonate (1.1 g) and copper(I) iodide (141 mg) in 1,4-dioxane (1.5 mL) was heated in a pressure vessel at 110° overnight and then cooled to room temperature, followed by adding Et acetate, adsorbing the resulting mixture on silica gel, and purification by silica gel chromatog. to give 8-amino-1-(4-phenoxyphenyl)imidazo[3,4-a]pyrazine derivative (IV) as yellow solid. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to aminoimidazopyrazine aminophenoxyphenylimidazopyrazine preparation btk protein kinase inhibitor, proliferative disease inflammatory disease inflammatory autoimmune disease treatment aminoimidazopyrazine and other aspects.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On March 15, 2015, Young, Wendy B.; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Crawford, James J.; Dambach, Donna; Gallion, Steve; Hymowitz, Sarah G.; Kropf, Jeffrey E.; Lee, Seung H.; Liu, Lichuan; Lubach, Joseph W.; Macaluso, Jen; Maciejewski, Pat; Maurer, Brigitte; Mitchell, Scott A.; Ortwine, Daniel F.; Di Paolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Sowell, C. Gregory; Wang, Xiaojing; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Currie, Kevin S. published an article.Recommanded Product: 87486-34-8 The title of the article was Potent and selective Bruton’s tyrosine kinase inhibitors: Discovery of GDC-0834. And the article contained the following:

SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 resulted in the clin. candidate GDC-0834, which retained the potency and selectivity of CGI-1746, but with much improved PK in preclin. animal models. Structure based design efforts drove this work as modifications to CGI-1746 were investigated at both the solvent exposed region as well as ‘H3 binding pocket’. However, in vitro metabolic evaluation of GDC-0834 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclin. species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclin. efficacy, a single dose IND was filed and GDC-0834 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, GDC-0834 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Recommanded Product: 87486-34-8

The Article related to bruton tyrosine kinase inhibitor gdc0834 preparation structure activity pharmacokinetics, amide hydrolysis, bruton’s tyrosine kinase, btk, gdc-0834, kinase inhibitor, rheumatoid arthritis, single dose ind and other aspects.Recommanded Product: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Nishihara, Ryo; Paulmurugan, Ramasamy; Nakajima, Takahiro; Yamamoto, Eiji; Natarajan, Arutselvan; Afjei, Rayhaneh; Hiruta, Yuki; Iwasawa, Naoko; Nishiyama, Shigeru; Citterio, Daniel; Sato, Moritoshi; Kim, Sung Bae; Suzuki, Koji published an article in 2019, the title of the article was Highly bright and stable NIR-BRET with blue-shifted coelenterazine derivatives for deep-tissue imaging of molecular events in vivo.Category: pyrazines And the article contains the following content:

Bioluminescence imaging (BLI) is one of the most widely used optical platforms in mol. imaging, but it suffers from severe tissue attenuation and autoluminescence in vivo. Here, we developed a novel BLI platform on the basis of bioluminescence resonance energy transfer (BRET) for achieving a ∼300 nm blue-to-near IR shift of the emission (NIR-BRET) by synthesizing an array of 18 novel coelenterazine (CTZ) derivatives, named “Bottle Blue (BBlue)” and a unique iRFP-linked RLuc8.6-535SG fusion protein as a probe. The best NIR-BRET was achieved by tuning the emission peaks of the CTZ derivatives to a Soret band of the iRFP. In mammalian cells, BBlue2.3, one of the CTZ derivatives, emits light that is ∼50-fold brighter than DBlueC when combined with RLuc8.6-535SG, which shows stable BL kinetics. When we used a caged version of BBLue2.3, it showed a BL half decay time of over 60 min while maintaining the higher signal sensitivity. This NIR BL is sufficiently brighter to be used for imaging live mammalian cells at single cell level, and also for imaging metastases in deep tissues in live mice without generating considerable autoluminescence. A single-chain probe developed based on this BLI platform allowed us to sensitively image ligand antagonist-specific activation of estrogen receptor in the NIR region. This unique optical platform provides the brightest NIR BLI template that can be used for imaging a diverse group of cellular events in living subjects including protein-protein interactions and cancer metastasis. 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).Category: pyrazines

The Article related to nir bioluminescence resonance energy transfer coelenterazine, bioluminescence imaging, bioluminescence resonance energy transfer (bret), blue-to-near infrared shift, coelenterazine derivatives, metastasis and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Pinto da Silva, Luis; Magalhaes, Carla M.; Nunez-Montenegro, Ara; Ferreira, Paulo J. O.; Duarte, Diana; Rodriguez-Borges, Jose E.; Vale, Nuno; Esteves da Silva, Joaquim C. G. published an article in 2019, the title of the article was Study of the combination of self-activating photodynamic therapy and chemotherapy for cancer treatment.Category: pyrazines And the article contains the following content:

Cancer is a very challenging disease to treat, both in terms of treatment efficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Anal. of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable. 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).Category: pyrazines

The Article related to breast neoplasm cell tamoxifen photodynamic therapy chemotherapy, anticancer drug, breast cancer, chemiluminescence, chemotherapy, multidrug combinations, photodynamic therapy, photosensitizer, prostate cancer and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Sousa, Joao; Magalhaes, Carla M.; Gonzalez-Berdullas, Patricia; Esteves da Silva, Joaquim C. G.; Pinto da Silva, Luis published an article in 2022, the title of the article was Comparative Investigation of the Chemiluminescent Properties of a Dibrominated Coelenterazine Analog.Recommanded Product: 55779-48-1 And the article contains the following content:

Chemi- and bioluminescence are remarkable light-emitting phenomena, in which thermal energy is converted into excitation energy due to a (bio)chem. reaction. Among a wide variety of chemi-/bioluminescent systems, one of the most well-known and studied systems is that of marine imidazopyrazinones, such as Coelenterazine and Cypridina luciferin. Due to the increasing usefulness of their chemi-/bioluminescent reactions in terms of imaging and sensing applications, among others, significant effort has been made over the years by researchers to develop new derivatives with enhanced properties. Herein, we report the synthesis and chemiluminescent characterization of a novel dibrominated Coelenterazine analog. This novel compound consistently showed superior luminescence, in terms of total light output and emission lifetime, to natural imidazopyrazinones and com. available analogs in aprotic media, while being capable of yellow light emission. Finally, this new compound showed enhanced chemiluminescence in an aqueous solution when triggered by superoxide anion, showing potential to be used as a basis for optimized probes for reactive oxygen species. In conclusion, bromination of the imidazopyrazinone scaffold appears to be a suitable strategy for obtaining Coelenterazines with enhanced properties. 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: 55779-48-1

The Article related to dibrominated coelenterazine comparative investigation chemiluminescent property, cypridina luciferin, bioluminescence, chemiluminescence, coelenterazine, coelenterazine analogues, luminescence, superoxide anion and other aspects.Recommanded Product: 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Kanie, Shusei; Komatsu, Mami; Mitani, Yasuo published an article in 2020, the title of the article was Luminescence of Cypridina luciferin in the presence of human plasma alpha 1-acid glycoprotein.Computed Properties of 55779-48-1 And the article contains the following content:

The enzyme Cypridina luciferase (CLase) enables Cypridina luciferin to emit light efficiently through an oxidation reaction. The catalytic mechanism on the substrate of CLase has been studied, but the details remain to be clarified. Here, we examined the luminescence of Cypridina luciferin in the presence of several proteins with drug-binding ability. Luminescence measurements showed that the mixture of human plasma alpha 1-acid glycoprotein (hAGP) and Cypridina luciferin produced light. The total value of the luminescence intensity over 60 s was over 12.6-fold higher than those in the presence of ovalbumin, human serum albumin, or bovine serum albumin. In the presence of heat-treated hAGP, the luminescence intensity of Cypridina luciferin was lower than in the presence of intact hAGP. Chlorpromazine, which binds to hAGP, showed an inhibitory effect on the luminescence of Cypridina luciferin, both in the presence of hAGP and a recombinant CLase. Furthermore, BlastP anal. showed that hAGP had partial amino acid sequence similarity to known CLases in the region including amino acid residues involved in the drug-binding ability of hAGP. These findings indicate enzymol. similarity between hAGP and CLase and provide insights into both the enzymol. understanding of CLase and development of a luminescence detection method for hAGP. 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 cypridina luciferin plasma alpha 1 acid glycoprotein luminescence, cypridina luciferase, cypridina luciferin, bioluminescence, cypridinid luciferase, cypridinid luciferin, human plasma alpha 1-aicd glycoprotein and other aspects.Computed Properties of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On March 8, 2012, Currie, Kevin S.; Wang, Xiaojing; Young, Wendy B. published a patent.Product Details of 87486-34-8 The title of the patent was Preparation of pyridinones and pyrazinones as Btk kinase inhibitors for treating inflammation, immunological disorders, cancer, and other diseases. And the patent contained the following:

Pyridinone and pyrazinone compounds of Formula I (wherein R1 is substituted isoindolinone, thienopyrrolone, or pyrrolothiazolone; R2 is H, Me, or CF3; ring B is ring B is Ph, 5-6 membered heteroaryl, or 8-11 membered heterocyclyl; R3 is H, halo, cyano, etc.; R6 is H, Me, F, etc.; R7 is H, Me F, etc.; R8 is H, Me, CF3, etc.; V is CH or N) including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase are claimed. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathol. conditions, are disclosed. Synthetic procedures for preparing I are exemplified. Example compound II, prepared in a multistep synthesis that culminated in the cyclization of III, had an IC50 of 0.0364 in a standard biochem. Btk kinase assay. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Product Details of 87486-34-8

The Article related to preparation pyridinone pyrazinone btk kinase inhibitor therapy diagnosis, immune disorder treatment pyridinone pyrazinone btk kinase inhibitor, inflammation cancer treatment pyridinone pyrazinone btk kinase inhibitor and other aspects.Product Details of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On January 31, 2021, Connick, J. Patrick; Reed, James R.; Cawley, George F.; Backes, Wayne L. published an article.Formula: C26H21N3O3 The title of the article was Heteromeric complex formation between human cytochrome P450 CYP1A1 and heme oxygenase-1. And the article contained the following:

P 450 and heme oxygenase-1 (HO-1) receive their necessary electrons by interaction with the NADPH-cytochrome P 450 reductase (POR). As the POR concentration is limiting when compared with P 450 and HO-1, they must effectively compete for POR to function. In addition to these functionally required protein-protein interactions, HO-1 forms homomeric complexes, and several P450s have been shown to form complexes with themselves and with other P450s, raising the question, ‘How are the HO-1 and P 450 systems organized in the endoplasmic reticulum’. Recently, CYP1A2 was shown to associate with HO-1 affecting the function of both proteins. The goal of this study was to determine if CYP1A1 formed complexes with HO-1 in a similar manner. Complex formation among POR, HO-1, and CYP1A1 was measured using bioluminescence resonance energy transfer, with results showing HO-1 and CYP1A1 form a stable complex that was further stabilized in the presence of POR. The POR•CYP1A1 complex was readily disrupted by the addition of HO-1. CYP1A1 also was able to affect the POR•HO-1 complex, although the effect was smaller. This interaction between CYP1A1 and HO-1 also affected function, where the presence of CYP1A1 inhibited HO-1-mediated bilirubin formation by increasing the KPOR•HO-1m without affecting the Vappmax. In like manner, HO-1 inhibited CYP1A1-mediated 7-ethoxyresorufin dealkylation by increasing the KPOR•CYP1A1m. Based on the math. simulation, the results could not be explained by a model where CYP1A1 and HO-1 simply compete for POR, and are consistent with the formation of a stable CYP1A1•HO-1 complex that affected the functional characteristics of both moieties. 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).Formula: C26H21N3O3

The Article related to heteromeric complex human cytochrome p450 cyp1a1 heme oxygenase, bioluminescence resonance energy transfer, cytochrome p450, heme oxygenase-1, membrane proteins, nadph-cytochrome p450 reductase, protein–protein interactions and other aspects.Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On June 12, 2019, Yeh, Hsien-Wei; Ai, Hui-Wang published an article.SDS of cas: 55779-48-1 The title of the article was Development and Applications of Bioluminescent and Chemiluminescent Reporters and Biosensors. And the article contained the following:

A review. Although fluorescent reporters and biosensors have become indispensable tools in biol. and biomedical fields, fluorescence measurements require external excitation light, thereby limiting their use in thick tissues and live animals. Bioluminescent reporters and biosensors may potentially overcome this hurdle because they use enzyme-catalyzed exothermic biochem. reactions to generate excited-state emitters. This review first introduces the development of bioluminescent reporters, and next, their applications in sensing biol. changes in vitro and in vivo as biosensors. Lastly, we discuss chemiluminescent sensors that produce photons in the absence of luciferases. This review aims to explore fundamentals and exptl. insights and to emphasize the yet-to-be-reached potential of next-generation luminescent reporters and biosensors. 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).SDS of cas: 55779-48-1

The Article related to review bioluminescent chemiluminescent reporter biosensor, bret, bioluminescence, bioluminescence resonance energy transfer, chemiluminescence, fluorescence, genetically encoded biosensor, in vivo imaging, luciferase, luciferin and other aspects.SDS of cas: 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem