Month: October 2022

On February 17, 2022, Chen, Yi published a patent.SDS of cas: 87486-34-8 The title of the patent was Preparation of heterocyclic compounds as BTK inhibitors, and dosage form compositions comprising an inhibitor of BTK and mutants thereof. And the patent contained the following:

Provided herewith are pharmaceutical tablet compositions comprising an organic acid (such as fumaric acid) and a compound of formula I, or an N-oxide thereof, solvate, polymorph, tautomer, stereoisomer, an isotopic form, or a prodrug of said compound of formula I or N-oxide thereof: wherein the compound of formula I is an inhibitor of Bruton’ s tyrosine kinase. Compounds of formula I wherein Q3 is 5-membered heteroaryl; m and n are independently 0, 1, 2, 3 and 4; R1 and R5 are independently H, D, alkyl,spiroalkyl, alkenyl, etc.; and their tablet compositions comprising organic acids, N-oxides, polymorphs, tautomers, stereoisomers, isotopic forms, and prodrugs, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were formulated as tablets and tested for pharmacokinetic properties (data given). The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).SDS of cas: 87486-34-8

The Article related to heterocyclyl preparation btk inhibitor dosage form, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.SDS of cas: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On June 7, 2007, Mulvihill, Kristen Michelle; Castelhano, Arlindo L. published a patent.Category: pyrazines The title of the patent was Process for the preparation of substituted imidazo[1,5-a]pyrazines. And the patent contained the following:

The title compounds [I; X = Cl, Br, I; e.g., 3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone] are prepared by the halogenation of 3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone with either N-chloro-, N-bromo-, or N-iodosuccinimide (e.g., NBS) in a compatible solvent (e.g., DMF) at 0-60°. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Category: pyrazines

The Article related to bromochloroimidazopyrazinylcyclobutanone preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 10, 2013, Crawford, James John; Ortwine, Daniel Fred; Wei, Binqing; Young, Wendy B. published a patent.Recommanded Product: 87486-34-8 The title of the patent was Heteroarylpyridone and azapyridone compounds as inhibitors of BTK activity and their preparation. And the patent contained the following:

The invention relates to heteroarylpyridone and azapyridone compounds of formula I and stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. 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. Compounds of formula I wherein X1is CR1 and N; X2 is CR2 and N; X3 is CR3 and N, where one or two of X1 – X2 are N; R1, R2 and R4 are independently H, F, Cl, NH2, etc.; R4 is H, F, Cl, CN, CH2OH, etc.; R5 is (un)substituted C6-20 aryl, C3-12 carbocyclyl, C1-20 heteroaryl, etc.; R6 is H, Me, Et, etc.; R7 is (un)substituted tricyclic azacyclyl; Y1 and Y2 are independently CH and N, provided that not both of Y1 and Y2 are N; and stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). All the invention compounds were evaluated for their BTK inhibitory activity. From the assay, it was determined that compound II exhibited IC50 value of 0.132 μM. 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 heteroarylpyridone azapyridone preparation btk inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Recommanded Product: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 31, 1983, Vekemans, J.; Pollers-Wieers, C.; Hoornaert, G. published an article.SDS of cas: 87486-34-8 The title of the article was A new synthesis of substituted 2(1H)-pyrazinones. And the article contained the following:

The hydrohalides of 2-sec-aminoalkanenitriles on treatment with oxalyl halides in o-Cl2C6H4 at 80-100° give 3,5-dihalo-2(1H)-pyrazinones, e.g. I, of which the 3-halo substituent is easily replaced by nucleophiles. A reaction mechanism for the pyrazinone synthesis is proposed. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).SDS of cas: 87486-34-8

The Article related to pyrazinone, aminoalkanenitrile cyclization oxalyl chloride, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.SDS of cas: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On January 15, 2009, Barr, Sharon; Buck, Elizabeth; Eyzaguirre, Alexandra; Russo, Suzanne; Bhagwat, Shripad published a patent.Electric Literature of 936901-72-3 The title of the patent was Preparation of imidazo[1,5-a]pyrazin-8-amine for use in combination therapy of cancers and cancer metastasis. And the patent contained the following:

The present invention provides a method for treating tumors or tumor metastases in patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an anti-cancer agents or treatment that elevates pAkt levels in tumor cells and mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, or ionizing radiation. The invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of the anti-cancer agent melphalan or 5-FU, and mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The invention also provides a pharmaceutical composition comprising an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. 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. The invention compounds were evaluated in various biol. tests (some data given). The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Electric Literature of 936901-72-3

The Article related to imidazopyrazinamine preparation mtor kinase inhibitor treatment cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Electric Literature of 936901-72-3

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

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 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 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 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