Tag: 200-300

On June 2, 2016, Hotta, Daido; Sakurada, Isao; Ogawa, Kouki; Sasano, Kota published a patent.Application of 87486-34-8 The title of the patent was Preparation of diazabicyclic compounds as orexin receptor antagonists. And the patent contained the following:

Title compounds I [n = 1 or 2; ring A = aryl or heteraryl (wherein aryl and heteroaryl are optionally substituted with R1); ring B = Ph or monocyclic heteroaryl (wherein Ph and heteroaryl are optionally substituted with R2); L = halo, cycloalkyl, alkoxy, etc.; L is an adjacent substituent to A-bicycle-CO-; R1 = independently halo, alkyl, alkenyl, etc.; R2 = independently halo, alkyl, alkenyl, etc.; or pharmaceutically acceptable salts or solvates thereof] were prepared For example, to a solution of II [R = H] (22 mg), Q1-OH (20 mg) and Et3N (42 μL) in DMF (0.50 mL) was added HATU (46 mg), the resulting mixture was stirred at room temperature for 2 h to give compound II [R = Q1]. (29 mg). In human orexin receptor antagonistic activity test, the invention compounds, e.g., II [R = Q2], showed IC50 of ≤40 nmol/L for orexin receptor 1. Compounds I are claimed useful for the treatment of sleep disorders. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Application of 87486-34-8

The Article related to diazabicycle preparation orexin receptor antagonist, sleep disorder treatment diazabicycle orexin receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Application of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On January 25, 2018, Hotta, Daido; Sakurada, Isao; Ogawa, Koki; Sasano, Kota published a patent.Recommanded Product: 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of diazabicyclic compounds as orexin receptor antagonists. And the patent contained the following:

Title compounds I [n = 1 or 2; ring A = aryl or heteraryl (wherein aryl and heteroaryl are optionally substituted with R1); ring B = Ph or monocyclic heteroaryl (wherein Ph and heteroaryl are optionally substituted with R2); L = halo, cycloalkyl, alkoxy, etc.; L is an adjacent substituent to A-bicycle-CO-; R1 = independently halo, alkyl, alkenyl, etc.; R2 = independently halo, alkyl, alkenyl, etc.; or pharmaceutically acceptable salts or solvates thereof] were prepared For example, to a solution of II [R = H] (22 mg), Q1-OH (20 mg) and Et3N (42 μL) in DMF (0.50 mL) was added HATU (46 mg), the resulting mixture was stirred at room temperature for 2 h to give compound II [R = Q1]. (29 mg). In human orexin receptor antagonistic activity test, the invention compounds, e.g., II [R = Q2], showed IC50 of ≤40 nmol/L for orexin receptor 1. Compounds I are claimed useful for the treatment of sleep disorders. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Recommanded Product: 3,5-Dibromo-1-methylpyrazin-2(1H)-one

The Article related to diazabicycle preparation orexin receptor antagonist, sleep disorder treatment diazabicycle orexin receptor antagonist, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Recommanded Product: 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On January 7, 2010, Dewdney, Nolan James; Lou, Yan; Sjogren, Eric Brian; Soth, Michael; Sweeney, Zachary Kevin published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Phenylpyrazinones derivatives as kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of inflammation and autoimmune diseases. And the patent contained the following:

The invention provides 5-phenyl-1H-pyrazin-2-one derivatives of formula I which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and autoimmune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions comprising compounds of formula I and at least one carrier, diluent or excipient. Compounds of formula I wherein the dotted bond is either a single or a double bond; R is H, R1, -R1-R2-R3, -R1-R3 and -R2-R3; R1 is (un)substituted (hetero)aryl and (un)substituted (hetero)cycloalkyl; R2 is CO, COO, (CH2)1-3-COO, CONH2 and derivatives, (CH2)1-3, O(CH2)1-3, etc.; R3 is H, (un)substituted lower (hetero)alkyl, (un)substituted lower alkoxy, amino, (un)substituted (hetero)aryl, (un)substituted arylalkyl, etc.; A is (un)substituted CH2, NH and N; B is CH and N; D is -C(O)- and -S(O2)-; Q is (un)substituted CH2 and NH; Y1 is H and lower alkyl; Y2 is H, halo and (un)substituted lower alkyl; n is 0-3; each Y21 is independently halo, (un)substituted lower alkyl, OH, lower alkoxy and amino; each Y3 is independently halo and (un)substituted lower alkyl; m is 0-1; Y4 is H, halo, (un)substituted lower alkyl, (un)substituted lower cycloalkyl, amino and derivatives; and their pharmaceutically acceptable salts thereof, are claimed. All the invention compounds were evaluated for their kinase inhibitory activity. From the assay, it was determined that example compound II exhibited the IC50 value of 0.01 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 phenylpyrazinones derivative preparation kinase inhibitor treatment inflammation autoimmune disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 22, 2019, Chen, Yi published a patent.Category: pyrazines The title of the patent was Preparation of cyclopentapyrrolopyrazine derivatives as inhibitors of Btk and mutants thereof. And the patent contained the following:

The title compounds I [Q1 = 5-6 membered aryl or heteroaryl; Q2 = 5-7 membered heterocycloalkyl, or heteroaryl; Q3 = 5-membered heteroaryl; each of W, X, Y, Z1, independently, = C(Ra), or N; each of R1, and R5, independently, = H, D, alkyl, etc.; R2 = H or alkyl; R3 = H, halo, alkyl, haloalkyl, or hydroxyalkyl; R4 = H, halo, alkyl; two of R1 groups, taken together with the atom to which they are attached, may optionally form (un)substituted cycloalkyl or heterocycloalkyl; two of R5 groups, taken together with the atom to which they are attached, may optionally form (un)substituted cycloalkyl or heterocycloalkyl; Ra = H, D, alkyl, etc.; each of m, n = (independently) 0-4; Warhead = CH:CH2, CH:CHCH2NMe2, CCMe], useful for treating a neoplastic disease, autoimmune disease, and inflammatory disorder, were prepared E.g., a multi-step synthesis of N-[5-({6-[2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3-(hydroxymethyl)pyridin-4-yl]-4-methyl-3-oxo-3,4-dihydropyrazin-2-yl}amino)-2-(4-methylpiperazin-1-yl)phenyl]acrylamide, starting from 4-fluoro-3-nitroaniline and 1-methylpiperazine, was described. Representative compounds I were evaluated in the biochem. enzymic assay (IC50) against WT and C481S BTK (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).Category: pyrazines

The Article related to cyclopentapyrrolopyrazine preparation btk inhibitor antitumor antiinflammatory autoimmune disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On April 8, 2021, Chen, Yi published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of heterocyclic compounds as inhibitors of Btk and mutants thereof. And the patent contained the following:

This invention relates to the title compounds I [Q0 = 5-9 membered aryl or heteroaryl; Q1 = 5-9 membered aryl or heteroaryl; Q2 = 5-7 membered heterocycloalkyl; Q3 = 5-membered heteroaryl; Q4 = 6-membered heteroaryl; W = C(O) or SO2; Z = NH or O; Warhead = C(R9):CHR8 or CCR10; each of R0, R1, R5-R10 = (independently) H, D, alkyl, etc.; R3 = H, halo, alkyl, haloalkyl, hydroxyalkyl; R4 = H, halo, alkyl; or R0 and R1 groups, taken together with the atom to which they are attached, may optionally form (un)substituted cycloalkyl or heterocycloalkyl; or two of R1 groups, taken together with the atom to which they are attached, may optionally form (un)substituted cycloalkyl or heterocycloalkyl; or two of R5 groups, taken together with the atom to which they are attached, may optionally form (un)substituted cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; etc.; each of i, j, m, n = (independently) 0-4] or pharmaceutically acceptable salts thereof, useful for treating a neoplastic disease, autoimmune disease, and inflammatory disorder. E.g., a multi-step synthesis of N-(5-((6-(2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)-3-(hydroxymethyl)pyridin-4-yl)-4-methyl-3-oxo-3,4-dihydropyrazin-2-yl)amino)-2-(4-methylpiperazin-1-yl)phenyl)acrylamide, starting from 4-fluoro-3-nitroaniline and N-methylpiperazine, was described. Exemplified compounds I were tested for their Btk inhibitory activity (data given for representative compounds I). 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 heterocyclic compound preparation btk inhibitor antitumor antiinflammatory autoimmune disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 26, 2021, Dai, Guangxiu; Xiao, Kun published a patent.Synthetic Route of 87486-34-8 The title of the patent was Preparation of heteroaryl heterocyclic compounds as BTK inhibitors for the treatment of cancer, inflammatory and autoimmune diseases. And the patent contained the following:

The invention is related to the preparation of compounds I [X1, X2 = independently CH, N; or X1 = N, X2 is CR14; R14 = C1-6 alkyl; X3, X4 = independently C or N; Y1, Y2 = independently CR10, N; R10 = H, D, halo, CN, etc.; R1, R2 = independently , H, D, halo, C1-6 alkyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl; or R1CCR2 form a ring selected from cyclohexane, (un)substituted cyclopentane, benzene, pyridine, etc.; R3 = H, D, halo, C1-6 haloalkyl; R4 = H, CHO, CONH2, halo, CN, 3-hydroxyoxetan-3-yl, etc.; Cy = II, III; R11 = H, C1-6 alkyl, C3-6 cycloalkyl, wherein the C1-6 alkyl is optionally substituted with one or more deuterium or halo; U, V, W = independently N, CR12; R12 = H, D, halo; R5 = H, (un)substituted alkoxycarbonyl, Ph, Ph, 5-6 membered monocyclic heteroaryl, 8-10 membered bicyclic heteroaryl, etc.; with provisos], their pharmaceutically acceptable salts, solvates, racemic mixtures, enantiomers, a diastereomers and tautomers, to a method of in vivo or in vitro inhibiting the activity of BTK their use for the treatment of related diseases, especially cancer, inflammatory and autoimmune diseases and pharmaceutical compositions containing them. Thus, IV was prepared by Pd-coupling of 5-bromo-3-[[5-[ethyl(2-methoxyethyl)amino]pyridin-2-yl]amino]-1-methylpyridin-2(1H)-one (preparation given) with [3-(2-acetoxyethyl)-2-(7,7-dimethyl-1-oxo-1,6,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2-yl)pyridin-4-yl]boronic acid (preparation given) and basic hydrolysis of the resulting acetate. V (characterization data given) inhibited BTK in a biochem. assay (IC50 = 0.008μM) and in Ramos cells (IC50 = 0.004μM). V showed better pharmacokinetic parameters than that of the reference GDC-0853, displayed a dose-dependent antitumor activity in the TMD8 s.c. xenograft model, and complete tumor regression would be achievable by continuous daily dosing of compound V at 30 mg/kg. The therapeutic effect of V on a rat arthritis model induced by type II collagen was studied (data given). 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 heteroaryl heterocycle preparation btk inhibitor antitumor inflammation autoimmune disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Synthetic Route of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 1, 2019, Gray, Nathanael S.; Wang, Jinhua; Dobrovolsky, Dennis published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of heterocycles as bifunctional compounds that targeting degradation of Bruton’s tyrosine kinase (BTK) by conjugation of BTK inhibitors with E3 ligase ligand for the treatment of BTK-mediated diseases. And the patent contained the following:

The invention relates to preparation of bifunctional compounds of formula (Targeting Ligand-Linker-Degron) wherein the Targeting Ligand is capable of binding to BTK; 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 an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton’s tyrosine kinase (BTK). The example compound I was prepared via three-steps synthetic procedure (procedure given). The present application also relates to methods for the targeted degradation of BTK through the use of bifunctional compounds 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. 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 dioxoindoline piperazine benzamide preparation btk modulator disease treatment prophylaxis, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 31, 2012, Sato, Nobuhiro; Fukuya, Shunsuke published an article.COA of Formula: C6Br2N4 The title of the article was Synthesis of 3,6-dibromopyrazine-2,5-dicarbonitrile. And the article contained the following:

Sym. functionalized 3,6-dibromopyrazine-2,5-dicarbonitrile was synthesized in 3 or 4 steps from 3-aminopyrazinecarbonitrile or its 6-bromo derivative The experimental process involved the reaction of 3,6-Dibromopyrazine-2,5-dicarbonitrile(cas: 1391026-27-9).COA of Formula: C6Br2N4

The Article related to pyrazinenitrile bromination cyanation, bromopyrazinedicarbonitrile preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.COA of Formula: C6Br2N4

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 11, 2020, Yang, Shengyong; Li, Linli published a patent.Electric Literature of 87486-34-8 The title of the patent was Anti-influenza small molecule compound and preparation method and application thereof. And the patent contained the following:

Preparation and anti-influenza activity of amino(fluoropyrrolo[2,3-b]pyridinyl)pyrazinones represented by I. In particular, I is a pharmaceutically acceptable salt, or stereoisomer or solvate thereof, or its prodrugs, or its metabolites: [wherein X is selected from CR4, N; Y is selected from CR5R6, NR7, O, S; R4, R5, R6 and R7 can be independently selected from H, C1~6 alkyl substituted with 0-4 R8, 3-8 membered cycloalkyl substituted with 0-4 R9, aryl or heteroaryl substituted with 0-4 R10; R8 is selected from 3~8 membered cycloalkyl, halogen, carboxyl, 3~8 membered (un)saturated heterocyclic group, (aryl/heteroaryl) substituted with 0~4 R11; R9 is selected from C1~6 alkyl, halogen; R10 is selected from C1~6 alkyl, C1~4 alkoxy, halogen substituted by 0~4 R12]. Further [R11 is selected from C1~6 alkyl substituted by 0~4 R12′, halogen; R12 and R12′ are independently selected from halogen, hydroxyl, amino; R2 is selected from H, C1~6 alkyl substituted with 0~4 R14 substituted 3~10 membered cycloalkyl, R13 is selected from 3~6-membered (un)saturated heterocyclic groups, carboxyl, aryl substituted with 0~3 R15, amide group, etc.; R14 is selected from C1~6 alkyl, carboxyl, R15 is selected from halogen, C1~4 alkoxy, R3 is selected from 5-fluoroindoline.]. The compound prepared by the present invention has a strong binding capacity with B2 protein, especially with PB2318-483 protein, so that it can block the transcription process of influenza RNA polymerase, thereby inhibiting the proliferation of influenza virus, hence can be used to prepare drugs against influenza virus. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Electric Literature of 87486-34-8

The Article related to fluoropyrrolopyridinyl aminopyrazinone preparation anti influenza activity, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Electric Literature of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On September 20, 2007, Buck, Elizabeth A.; Griffin, Graeme; Barr, Sharon M. published a patent.Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the patent was Imidazo[1,5-a]pyrazin-8-amine in combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors. And the patent contained the following:

The invention provides a method for manufacturing a medicament intended for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in combination with an EGFR kinase inhibitor, characterized in that an mTOR inhibitor is used, and wherein the inhibitors are intended for administration either simultaneously or sequentially, and with or without administration of addnl. agents or treatments, such as other anti-cancer drugs or radiation therapy. The invention also provides a method for manufacturing a medicament intended for treating tumors or tumor metastases in a patient in combination of an EGFR kinase inhibitor, characterized in that an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases is used, and wherein the inhibitors are intended for administration either simultaneously or sequentially, and with or without administration of addnl. agents or treatments, such as other anti-cancer drugs or radiation therapy. The invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA). Example compound I was prepared by cross-coupling of 8-amino-3-cyclobutyl-1-iodoimidazol[3,4-a]pyrazine with 5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1H-indole. All the invention compounds were evaluated for their EGFR kinase inhibitory activity (some data given). The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to imidazopyrazinamine preparation egfr kinase inhibitor treatment cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Safety of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem