Month: November 2022

On August 31, 2021, Crespo, Emmanuel L.; Bjorefeldt, Andreas; Prakash, Mansi; Hochgeschwender, Ute published an article.Safety of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one The title of the article was Bioluminescent optogenetics 2.0: harnessing bioluminescence to activate photosensory proteins in vitro and in vivo. And the article contained the following:

Bioluminescence – light emitted by a luciferase enzyme oxidizing a small mol. substrate, a luciferin – has been used in vitro and in vivo to activate light-gated ion channels and pumps in neurons. While this bioluminescent optogenetics (BL-OG) approach confers a chemogenetic component to optogenetic tools, it is not limited to use in neuroscience. Rather, bioluminescence can be harnessed to activate any photosensory protein, thus enabling the manipulation of a multitude of light-mediated functions in cells. A variety of luciferase-luciferin pairs can be matched with photosensory proteins requiring different wavelengths of light and light intensities. Depending on the specific application, efficient light delivery can be achieved by using luciferase-photoreceptor fusion proteins or by simple co-transfection. Photosensory proteins based on light-dependent dimerization or conformational changes can be driven by bioluminescence to effect cellular processes from protein localization, regulation of intracellular signaling pathways to transcription. The protocol below details the exptl. execution of bioluminescence activation in cells and organisms and describes the results using bioluminescence-driven recombinases and transcription factors. The protocol provides investigators with the basic procedures for carrying out bioluminescent optogenetics in vitro and in vivo. The described approaches can be further extended and individualized to a multitude of different exptl. paradigms. 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).Safety of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

The Article related to bioluminescent optogenetics harnessing bioluminescence photosensory protein, Biochemical Methods: Spectral and Related Methods and other aspects.Safety of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Yu, Xiaowen; Scott, Daniel; Dikici, Emre; Joel, Smita; Deo, Sapna; Daunert, Sylvia published an article in 2019, the title of the article was Multiplexing cytokine analysis: towards reducing sample volume needs in clinical diagnostics.Formula: C26H21N3O3 And the article contains the following content:

The trend for improved more precise diagnostics and management of disease heavily relies on the measurement of panels of biomarkers in physiol. samples of patients. Ideally, the ultimate goal would be to detect as many clin. relevant biomarkers as possible in a single drop of blood, achieving quick, sensitive, reproducible, and affordable detection in small volume physiol. samples. Bioluminescent (BL) proteins provide many of the desired characteristics required for such labels, including detection at extremely low concentrations, no interference from physiol. fluids leading to excellent detection limits, and compatibility with many miniaturized systems. However, to date the use of BL proteins has been restricted by their limited multiplexing capabilities. BL proteins typically exhibit a single emission profile and decay kinetics making the simultaneous detection of multiple analytes difficult. Recent progresses in this area include the use of two different engineered luminescent proteins to achieve resolved signals via one-dimensional time resolution This approach, however, to date only lead to a dual analyte detection. Herein, we have demonstrated that using a two-dimensional approach that combines both temporal and spatial resolution, we can expand the multiplexing capabilities of bioluminescent proteins. To that end, the photoprotein aequorin (AEQ) has been employed for the simultaneous detection of three sep. analytes in a single well, differentiated through the use of three discrete time/wavelength windows. Through a combination of site-specific mutations and synthetic coelenterazines “semi-synthetic” AEQ variants have been developed with altered emission profiles and decay kinetics. In this study, two AEQ mutant proteins were genetically conjugated to three pro-inflammatory cytokines (tumor necrosis factor alpha, interleukins 6 and 8) resulting in AEQ-labeled cytokines. These fusion proteins were combined with synthetic coelenterazines resulting in proteins with differing emission maxima and half-lives to allow for the simultaneous detection of all three cytokines in a single sample. The validity of the assay was demonstrated in serum by employing human physiol. samples and comparing our results with com. available individual tests for each of the three cytokines. 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 aequorin cytokine fusion protein coelenterazine blood analysis interleukin tnfalpha, Biochemical Methods: Spectral and Related Methods and other aspects.Formula: C26H21N3O3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 28, 2020, Ruffinatti, Federico Alessandro; Lomazzi, Samuela; Nardo, Luca; Santoro, Romualdo; Martemiyanov, Alexander; Dionisi, Marianna; Tapella, Laura; Genazzani, Armando A.; Lim, Dmitry; Distasi, Carla; Caccia, Massimo published an article.Synthetic Route of 55779-48-1 The title of the article was Assessment of a Silicon-Photomultiplier-Based Platform for the Measurement of Intracellular Calcium Dynamics with Targeted Aequorin. And the article contained the following:

Ca2+ is among the most important intracellular second messengers participating in a plethora of biol. processes, and the measurement of Ca2+ fluctuations is significant in the phenomenol. of the underlying processes. Aequorin-based Ca2+ probes represent an invaluable tool for reliable measurement of Ca2+ concentrations and dynamics in different subcellular compartments. However, their use is limited due to the lack on the market of ready-to-use, cost-effective, and portable devices for the detection and readout of the low-intensity bioluminescence signal produced by these probes. Silicon photomultipliers (SiPMs) are rapidly evolving solid-state sensors for low light detection, with single photon sensitivity and photon number resolving capability, featuring low cost, low voltage, and compact format. Thus, they may represent the sensors of choice for the development of such devices and, more in general, of a new generation of multipurpose bioluminescence detectors suitable for cell biol. studies. Ideally, a detector customized for these purposes must combine high dynamic range with high fidelity in reconstructing the light intensity signal temporal profile. The ability to perform aequorin-based intracellular Ca2+ measurements using a multipurpose, low-cost setup exploiting SiPMs as the sensors is demonstrated. SiPMs turn out to assure performances comparable to those exhibited by a custom-designed photomultiplier tube-based aequorinometer. Moreover, the flexibility of SiPM-based devices might pave the way toward routinely and wide scale application of innovative biophys. protocols. 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 silicon photomultiplier calcium dynamics aequorin, aequorin, bioluminescence, calcium signaling, live cell, silicon photomultipliers, Biochemical Methods: Spectral and Related Methods and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Abe, Masahiro; Nishihara, Ryo; Ikeda, Yuma; Nakajima, Takahiro; Sato, Moritoshi; Iwasawa, Naoko; Nishiyama, Shigeru; Paulmurugan, Ramasamy; Citterio, Daniel; Kim, Sung Bae; Suzuki, Koji published an article in 2019, the title of the article was Near-Infrared Bioluminescence Imaging with a through-Bond Energy Transfer Cassette.Electric Literature of 55779-48-1 And the article contains the following content:

A coelenterazine (CTZ) analog emitting near-IR (NIR) bioluminescence was synthesized for through-bond energy transfer (TBET)-based imaging modalities. The analog, named Cy5-CTZ, was prepared by conjugating cyanine-5 (Cy5) dye to CTZ through an acetylene linker. This novel derivative is intrinsically fluorescent and emits NIR-shifted luminescence upon reacting with an appropriate luciferase, the Renilla luciferase. This Cy5-CTZ substrate is optically stable in physiol. samples and rapidly permeabilize through the plasma membrane into the cytosolic compartment of live cells. 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 breast cancer fibroblast like cell nir bioluminescence imaging, bioluminescence, dyes/pigments, energy transfer, fluorescence, imaging agents, Biochemical Methods: Spectral and Related Methods and other aspects.Electric Literature of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 5, 2022, Chen, Yi published a patent.HPLC of Formula: 87486-34-8 The title of the patent was Synthesis of Pyridine BTK inhibitors treating cancers, autoimmune and inflammatory diseases. And the patent contained the following:

The synthesis of pyridine BTK inhibitors, I, wherein Q is a 5-9 membered aryl or heteroaryl ring; Q1 is a 5-7 membered heterocycloalkyl group; Q2 can be a 5-membered heteroaryl or Ph ring; Q3 can be a 6-membered heteroaryl group; Z can be absent, alkyl ether, amine, thioether, carbonyl, sulfonyl, sulfone, ester, or related moieties; L can be absent or an appropriate linker group; the warhead is an alkene or alkyne group; R can be independently H, D, alkyl, spiroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or related groups; R1 can be H, halo, alkyl, haloalkyl, or hydroxyalkyl; R2 can be H, halo, or low alkyl; treating cancers, autoimmune and inflammatory diseases. Of note, II was synthesized and tested in an in vitro dialysis assay WT BTK with an IC50 of 7.0 nM, in pharmacokinetics, xenograft and arthritis studies. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).HPLC of Formula: 87486-34-8

The Article related to pyridine btk inhibitor preparation anticancer autoimmune inflammatory, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.HPLC of Formula: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 31, 2018, Gray, Nathanael S.; Dobrovolsky, Dennis; Huang, Hai-Tsang published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Degradation of Bruton’s tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use. And the patent contained the following:

The present invention provides bifunctional compounds Targeting Ligand-Linker-Degron [I; the Targeting Ligand (TL) is capable of binding to one or more protein kinases (TL = II [X1 = NR3a or O; X2 = O or 1,4-piperazinediyl; each R1 = alkyl, haloalkyl, alkoxy, etc.; R2 = alkyl, haloalkyl, alkoxy, etc.; R3a and R3b = H, alkyl, haloalkyl; each R4 = alkyl, haloalkyl, alkoxy, etc.; n1 and n2 = 0-2; n3 = 0-4; n4 = 1-4], III [A and B = (un)substituted Ph or 5-6 membered heteroaryl containing 1-2 heteroatoms selected from N, S; Y2 = O or NR10a; Y3 = C(O)NR10b or NR10bC(O); Y4 = NR51 or, when B is bonded to Y4, N (wherein R51 = H, alkyl, haloalkyl, etc.); each R5 = alkyl, haloalkyl, alkoxy, etc.; R6 = H, alkyl, haloalkyl; each R7 = alkyl, haloalkyl, alkoxy, etc.; each R8 = alkyl, haloalkyl, alkoxy, etc.; R9 = alkyl, haloalkyl, alkoxy, etc.; R10a and R10b = H, alkyl or haloalkyl; or R8 and R10b together with the atoms to which they are attached form a 5-6 membered heterocycloalkyl or heteroaryl containing 1-2 heteroatoms selected from N, O, S; o1 and o2 = 0-3], etc.); the Linker is a group that covalently binds to the Targeting Ligand and the Degron; and the Degron is capable of binding to a ubiquitin ligase] or enantiomers, diastereomers, or stereoisomers thereof, or pharmaceutically acceptable salts, hydrates, solvates, or prodrugs thereof, which act as protein degradation inducing moieties for Bruton’s tyrosine kinase (BTK). Compound IV was prepared in a multi-step synthesis, starting from tert-Bu piperazine-1-carboxylate and 4-nitrobenzoic acid. The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds I that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK. Exemplified compounds I were tested for their BTK degradation in the cell assay (data given). Pharmaceutical composition comprising compound I was disclosed. 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 bifunctional compound preparation protein btk degradation inducer ubiquitin ligase, antitumor bifunctional compound preparation bruton’s tyrosine kinase btk inhibitor, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 31, 2018, Gray, Nathanael S.; Dobrovolsky, Dennis; Huang, Hai-Tsang published a patent.Application In Synthesis of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Degradation of Bruton’s tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand and methods of use. And the patent contained the following:

The present invention provides bifunctional compounds Targeting Ligand-Linker-Degron [I; the Targeting Ligand (TL) is capable of binding to one or more protein kinases (TL = II [B = (un)substituted Ph or 5-6 membered heteroaryl containing 1-2 heteroatoms selected from N, S; when Y1 is absent, B is bonded to a carbon atom or Y4 in III; Y1 = absent or C(O), wherein Y1 is bonded to a carbon atom or Y4 in III; Y2 = O or NR10a; Y3 = C(O)NR10b or NR10bC(O); Y4 = NR51 or, when Y1 is bonded to Y4 or when Y1 is absent and B is bonded to Y4, Y4 = N (wherein R51 = H, alkyl, haloalkyl, etc.); each R5 = alkyl, haloalkyl, alkoxy, etc.; R6 = H, alkyl, haloalkyl; each R7 = alkyl, haloalkyl, alkoxy, etc.; each R8 = alkyl, haloalkyl, alkoxy, etc.; R9 = alkyl, haloalkyl, alkoxy, etc.; R10a and R10b = H, alkyl or haloalkyl; o1, o2 or o3 = 0-3], etc.); the Linker is a group that covalently binds to the Targeting Ligand and the Degron; and the Degron is capable of binding to a ubiquitin ligase] or enantiomers, diastereomers, or stereoisomers thereof, or pharmaceutically acceptable salts, hydrates, solvates, or prodrugs thereof, which act as protein degradation inducing moieties for Bruton’s tyrosine kinase (BTK). Compound IV was prepared in a multi-step synthesis, starting from tert-Bu piperazine-1-carboxylate and 4-nitrobenzoic acid. The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds I that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK. Exemplified compound IV was tested and showed BTK degradation in the cell assay. Pharmaceutical composition comprising compound I was disclosed. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Application In Synthesis of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

The Article related to bifunctional compound preparation protein btk degradation inducer ubiquitin ligase, antitumor bifunctional compound preparation bruton’s tyrosine kinase btk inhibitor, Heterocyclic Compounds (One Hetero Atom): Pyridines and other aspects.Application In Synthesis of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On April 23, 2013, Blomgren, Peter A.; Brittelli, David R.; Currie, Kevin S.; Lee, Seung H.; Kropf, Jeffrey E.; Mitchell, Scott A.; Schmitt, Aaron C.; Wang, Xiaojing; Xu, Jianjun; Zhao, Zhongdong; Zhichkin, Pavel E. published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Certain substituted amides, method of making, and method of use thereof. And the patent contained the following:

The invention relates to compounds of the following Formula Iwherein R1, R2, Z, W, and D are defined herein, that inhibit Btk and therefore are useful in the treatment of diseases responsive to inhibition of Btk activity such as cancer. The invention also relates to pharmaceutical compositions comprising at least one compound of Formula I, together with at least one pharmaceutically acceptable vehicle chosen from carriers, adjuvants, and excipients, as well as methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/or B-cell activity are described, and methods for determining the presence of Btk in a sample. 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 methanobenzothiophene carboxamide preparation btk inhibitor, Heterocyclic Compounds (One Hetero Atom): Thiophenes and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On November 12, 2009, Blomgren, Peter A.; Brittelli, David R.; Currie, Kevin S.; Lee, Seung H.; Kropf, Jeffrey E.; Mitchell, Scott A.; Schmitt, Aaron C.; Wang, Xiaojing; Xu, Jianjun; Zhao, Zhongdong; Zhichkin, Pavel E. published a patent.Synthetic Route of 87486-34-8 The title of the patent was Preparation of methano- or ethanobenzo[b]thiophene-2-carboxamides and related analogous as BTK inhibitors. And the patent contained the following:

Title compounds I [R1 = methanobenzo[b]thiophene, ethanobenzo[b]thiophene, methanonaphthalene, etc.; R2 = H or CH3; Z = (un)substituted phenylene or pyridylidene; W = pyrrolo[2,3-b]pyridinyl, imidazo[4,5-b]pyridinyl, Isothiazolo[5,4-b]pyridinyl, etc.; D = NHR7; R7 = (un)substituted aryl or heteroaryl], and their pharmaceutically acceptable salts, solvates, chelates, noncovalent complexes, prodrugs, and mixtures, are prepared and disclosed as BTK inhibitors. Pharmaceutical compositions comprising at least one compound of I, together with at least one pharmaceutically acceptable vehicle chosen from carriers, adjuvants, and excipients. are described. Methods of treating patients suffering from certain diseases responsive to inhibition of BTK activity and/ or B-cell activity are described. E.g., II was prepared by amidation of 4,5,6,7-tetrahydro-4,7-methanobenzo[b]thiophene-2-carboxylic acid (preparation given) with 5-(3-amino-2-methylphenyl)-3-[[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino]-1-methylpyrazin-2(1H)-one (preparation given). Certain compounds of the invention exhibited both biochem. and cell-based activity in BTK kinase assay with IC50 value of ≤ 5 nM. 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 methanobenzothiophene carboxamide preparation btk inhibitor, Heterocyclic Compounds (One Hetero Atom): Thiophenes and other aspects.Synthetic Route of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On February 15, 2020, Hosseinnia, Maryam; Khalifeh, Khosrow; Jafarian, Vahab published an article.Synthetic Route of 55779-48-1 The title of the article was Polarity change of a representative helix in coelenterazin-binding cavity of mnemiopsin 2: Functional and structural consequences. And the article contained the following:

To evaluate the effect of a pos. charged residue at the end of the fourth helix on the function and stability of the folded state of mnemiopsin 2, Lys89 was replaced with Ala (K89A mutant). Its structural and functional features were investigated and compared with Wild type (WT) protein using a combination of theor. and exptl. procedures. The tertiary structures of WT and mutant photoproteins were made with MODELLER program, and were used for designing of mutation as well as explaining the results of exptl. measurements. Activity measurements showed that the initial intensity of light emission is reduced, but decay time is not changed upon mutation. K89A mutant exhibited more sensitivity to calcium ion than WT protein did. As compared to the pH 9 of WT, the optimum pH for the mutant increased to 9.25. According to the CD measurements at far UV region, the total amount of helical structure is not changed upon mutation; however, the helicity of chromophores is reduced in K89A mutant, demonstrating that the secondary structural elements in WT protein are more rigid. Heat-induced denaturation data showed that the stability of the WT is greater than mutant photoprotein by 2 kcal/mol. It appears that the higher value of the dipole momentum at the axis of fourth helix in WT photoprotein leads to strengthening of intra-mol. “head-to-tail” vs. “side-by-side” anti-parallel interaction between the third and fourth helixes. It was concluded that dipole-dipole interaction between the helixes are important factors in packaging of the substrate in the core structure of the photoprotein. 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 mnemiopsin 2 coelenterazin bioluminescence thermostability dipole, General Biochemistry: Proteins and Their Constituents and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem