Category: Pyrazines

On December 31, 2020, Tessler, Michael; Gaffney, Jean P.; Oliveira, Anderson G.; Guarnaccia, Andrew; Dobi, Krista C.; Gujarati, Nehaben A.; Galbraith, Moira; Mirza, Jeremy D.; Sparks, John S.; Pieribone, Vincent A.; Wood, Robert J.; Gruber, David F. published an article.Related Products of 55779-48-1 The title of the article was A putative chordate luciferase from a cosmopolitan tunicate indicates convergent bioluminescence evolution across phyla. And the article contained the following:

Pyrosomes are tunicates in the phylum Chordata, which also contains vertebrates. Their gigantic blooms play important ecol. and biogeochem. roles in oceans. Pyrosoma, meaning “fire-body”, derives from their brilliant bioluminescence. The biochem. of this light production is unknown, but has been hypothesized to be bacterial in origin. We found that mixing coelenterazine-a eukaryote-specific luciferin-with Pyrosoma atlanticum homogenate produced light. To identify the bioluminescent machinery, we sequenced P. atlanticum transcriptomes and found a sequence match to a cnidarian luciferase (RLuc). We expressed this novel luciferase (PyroLuc) and, combined with coelenterazine, it produced light. A similar gene was recently predicted from a bioluminescent brittle star, indicating that RLuc-like luciferases may have evolved convergently from homologous dehalogenases across phyla (Cnidaria, Echinodermata, and Chordata). This report indicates that a widespread gene may be able to functionally converge, resulting in bioluminescence across animal phyla, and describes and characterizes the first putative chordate luciferase. 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).Related Products of 55779-48-1

The Article related to pyrosoma atlanticum vertebrates transcriptomes bioluminescence bacteria, Nonmammalian Biochemistry: Classical Genetics and Phylogeny and other aspects.Related Products of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On December 31, 2021, Kanie, Shusei; Miura, Daisuke; Jimi, Naoto; Hayashi, Taro; Nakamura, Koji; Sakata, Masahiko; Ogoh, Katsunori; Ohmiya, Yoshihiro; Mitani, Yasuo published an article.Synthetic Route of 55779-48-1 The title of the article was Violet bioluminescent Polycirrus sp. (Annelida: Terebelliformia) discovered in shallow coastal waters of Noto Peninsula in Japan. And the article contained the following:

Terebellidae worms have large numbers of tentacles responsible for various biol. functions. Some Terebellidae worms whose tentacles emit light are found around the world, including exceptional violet-light-emitting Polycirrus spp. found in Europe and North America. However, there is no video-recorded observation of the luminous behavior of such unique species in nature, and the genetic information related to their ecol. are lacking. Here, for the first time, we video-recorded the violet-light-emitting behavior of an undescribed Japanese worm in its natural habitat. The worm was designated as Polycirrus sp. ISK based on morphol. observations, and the luminescence spectrum showed a peak at 444 nm, which is an exceptionally short wavelength for bioluminescence in a shallow coastal water environment. An anal. of differentially expressing genes based on sep. RNA-Seq anal. for the tentacles and the rest of body revealed the specific expression of genes that are probably involved in innate immunity in the tentacles exposed to predators. We also found a Renilla luciferase homologous gene, but coelenterazine was not detected in the worm extract by analyses using a liquid chromatog. and a recombinant Renilla luciferase. These results will promote an understanding of the ecol. and luminescence mechanisms of luminous Polycirrus spp. 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 violet bioluminescence terebelliformia shallow coastal water, Nonmammalian Biochemistry: Classical Genetics and Phylogeny and other aspects.Synthetic Route of 55779-48-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On September 30, 2020, Gunter, Julia; Wenger, Roland H.; Scholz, Carsten C. published an article.Recommanded Product: 55779-48-1 The title of the article was Inhibition of firefly luciferase activity by a HIF prolyl hydroxylase inhibitor. And the article contained the following:

The three hypoxia-inducible factor (HIF) prolyl-4-hydroxylase domain (PHD) 1-3 enzymes confer oxygen sensitivity to the HIF pathway and are novel therapeutic targets for treatment of renal anemia. Inhibition of the PHDs may further be beneficial in other hypoxia-associated diseases, including ischemia and chronic inflammation. Several pharmacol. PHD inhibitors (PHIs) are available, but our understanding of their selectivity and its chem. basis is limited. We here report that the PHI JNJ-42041935 (JNJ-1935) is structurally similar to the firefly luciferase substrate D-luciferin. Our results demonstrate that JNJ-1935 is a novel inhibitor of firefly luciferase enzymic activity. In contrast, the PHIs FG-4592 (roxadustat) and FG-2216 (ICA, BIQ, IOX3, YM 311) did not affect firefly luciferase. The JNJ-1935 mode of inhibition is competitive with a Ki of 1.36μM. D-luciferin did not inhibit the PHDs, despite its structural similarity to JNJ-1935. This study provides insights into a previously unknown JNJ-1935 off-target effect as well as into the chem. requirements for firefly luciferase and PHD inhibitors and may inform the development of novel compounds targeting these enzymes. 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 jnj1935 luciferase prolyl 4 hydroxylase domain inhibitor d luciferin, 2-oxoglutarate, dioxygenase, epigenetics, erythropoietin, hypoxia, kidney disease, Pharmacology: Drug Interactions and General Pharmacology and other aspects.Recommanded Product: 55779-48-1

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

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 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 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 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 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

Ishimoto, Tetsuya; Okada, Takuya; Fujisaka, Shiho; Yagi, Kunimasa; Tobe, Kazuyuki; Toyooka, Naoki; Mori, Hisashi published an article in 2022, the title of the article was A New Method for Albuminuria Measurement Using a Specific Reaction between Albumin and the Luciferin of the Firefly Squid Watasenia scintillans.Application In Synthesis of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one And the article contains the following content:

This study demonstrates that the luciferin of the firefly squid Watasenia scintillans, which generally reacts with Watasenia luciferase, reacted with human albumin to emit light in proportion to the albumin concentration The luminescence showed a peak wavelength at 540 nm and was eliminated by heat or protease treatment. We used urine samples collected from patients with diabetes to quantify urinary albumin concentration, which is essential for the early diagnosis of diabetic nephropathy. Consequently, we were able to measure urinary albumin concentrations by precipitating urinary proteins with acetone before the reaction with luciferin. A correlation was found with the result of the immunoturbidimetric method; however, the Watasenia luciferin method tended to produce lower albumin concentrations This may be because the Watasenia luciferin reacts with only intact albumin. Therefore, the quantification method using Watasenia luciferin is a new principle of urinary albumin measurement that differs from already established methods such as immunoturbidimetry and high-performance liquid chromatog. 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 watasenia albuminuria albumin luciferin immunoturbidimetry bioluminescence, watasenia scintillans, albumin, bioluminescence, diabetic nephropathy, luciferin, urine, Biochemical Methods: Other (Not Covered At Other Subsections) 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