Month: October 2022

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 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 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 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 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

Eremeeva, Elena V.; Jiang, Tianyu; Malikova, Natalia P.; Li, Minyong; Vysotski, Eugene S. published an article in 2020, the title of the article was Bioluminescent properties of semi-synthetic obelin and aequorin activated by coelenterazine analogue with modifications of C-2, C-6, and C-8 substituents.Reference of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one And the article contains the following content:

Investigated the specific bioluminescence activity, light emission spectra, stopped-flow kinetics and sensitivity to calcium of the semi-synthetic aequorins and obelins activated by novel coelenterazine analogs and the recently reported coelenterazine derivatives Several semi-synthetic photoproteins activated by the studied coelenterazine analogs displayed sufficient bioluminescence activities accompanied by various changes in the spectral and kinetic properties as well as in calcium sensitivity. The poor activity of certain semi-synthetic photoproteins might be attributed to instability of some coelenterazine analogs in solution and low efficiency of 2-hydroperoxy adduct formation. In most cases, semi-synthetic obelins and aequorins displayed different properties upon being activated by the same coelenterazine analog. The results indicated that the OH-group at the C-6 Ph ring of coelenterazine was important for the photoprotein bioluminescence and that the hydrogen-bond network around the substituent in position 6 of the imidazopyrazinone core was the reason of different bioluminescence activities of aequorin and obelin with certain coelenterazine analogs. 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).Reference of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

The Article related to benzyl imidazopyrazinone preparation sar obelin aequorin bioluminescence, aequorin, analogues, coelenterazine, obelin, photoprotein, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Reference of 8-Benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 19, 2011, Epstein, David M.; Jin, Meizhong; Mulvihill, Mark J. published a patent.Category: pyrazines The title of the patent was Preparation of deuterated heteroaryl compounds as tyrosine kinase inhibitors. And the patent contained the following:

The title compounds with general formula I [wherein X = independently N or C-A; Y = independently N or C; Z = N, C-H, C-D, or N-A; W = independently N, N=O, or C-B; G = Ph or pyridyl, either optionally substituted by one or more D or halogen atoms; R = absent, D, optionally substituted C1-10 alkyl, C3-10cycloalkyl, etc.; where A = independently H, D, halogen, CF3, etc.; B = Me, Et, H, D, etc.; with the proviso that at least one of Y and Z is N or N-A, at least one of W is N or N=O, and any hydrogen atom can be replaced by a D atom and the compound or salt is present as a material comprising at least one D atom in an abundance of at least about 10 %] or pharmaceutically acceptable salts thereof were prepared as inhibitors of IGF-1R and IR. For example, compound II was prepared in a multi-step synthesis. Compounds I may inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and prevention of various diseases and conditions such as hyperproliferative disorders such as cancers. 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 preparation deuterated tyrosine kinase inhibitor quinoline imidazole triazine pyrazine, human treatment cancer hyperproliferative disorder antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Category: pyrazines

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On September 21, 2006, Brittelli, David R.; Currie, Kevin S.; Darrow, James W.; Kropf, Jeffrey E.; Lee, Seung H.; Gallion, Steven L.; Mitchell, Scott A.; Pippin, Douglas A. I.; Blomgren, Peter A. published a patent.Electric Literature of 87486-34-8 The title of the patent was Preparation of substituted amides as Btk inhibitors. And the patent contained the following:

At least one chem. entity chosen from compounds I [R = (un)substituted cycloalkyl, aryl, heteroaryl; M = a bond, CH:CH; Q = CR10R11NR12, NR12CR10R11, NR13CO, CONR13, NR14CONR15 (wherein R10, R11 = H, alkyl, haloalkyl; R12-R15 = H, alkyl, haloalkyl, Ph, etc.); Z = (un)substituted phenylene, pyridylidene; W = (un)substituted heteroaryl other than imidazo[1,2-a]pyrazine; D = hydrogen bond donor other than hydrogen; with the provision] and pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, prodrugs, and mixtures thereof is described herein. E.g., a multi-step synthesis of II, starting from 3,5-dibromo-1H-pyridin-2-one, was given. Exemplified compounds I were tested in the Btk biochem. assay and certain of those compounds exhibited an IC50 value less than or equal to 1 μM. Some of the compounds I were also tested for inhibition of B-cell proliferation and T-cell proliferation. Pharmaceutical compositions comprising at least one chem. entity of the invention, together with at least one pharmaceutically acceptable vehicle chosen from carriers adjuvants, and excipients, are also described. Methods of treating patients suffering from certain diseases responsive to inhibition of Btk activity and/or B-cell activity are described. Methods for determining the presence of Btk in a sample are described. 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 amide preparation bruton’s tyrosine kinase btk inhibitor, b cell proliferation inhibitor amide preparation, t cell proliferation inhibitor amide preparation, 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 March 26, 2009, Blomgren, Peter A.; Currie, Kevin S.; Lee, Seung H.; Mitchell, Scott A.; Xu, Jianjun; Schmitt, Aaron C.; Zhao, Zhongdong; Zhichkin, Pavel E.; Stafford, Douglas G.; Kroft, Jeffrey E. published a patent.COA of Formula: C5H4Br2N2O The title of the patent was Preparation of pyrazinone substituted amides as Btk inhibitors. And the patent contained the following:

The title compounds I [X = N, CR2; Y = N, CR31; Z = N, CR3; provided that only one of X, Y and Z = N at a time; W = N, CH; V = CH, N; provided that one of W and V must be N and W and V are not both N; R1 = (un)substituted 4,5,6,7-tetrahydrobenzo[b]thien-2-yl, Ph, cyclohepta[b]thien-2-yl, etc.; R2 = H, Me, F, Cl, etc.; R21 = H, F; R3 = H, Me, CF3, F, etc.; R31 = H, Me, F, Cl, etc.; R4 = II (wherein m, n = 0-1; R5 = H, (un)substituted alkyl, cycloalkyl; R6 = H, (un)substituted alkyl; or NR5R6 = (un)substituted 4-6 membered cyclic ring having 0-1 addnl. N, S or O atoms; R7 = H, (un)substituted alkyl, cycloalkyl; R8 = H, (un)substituted alkyl; or NR7R8 = (un)substituted 4-6 membered cyclic ring having 0-1 addnl. N, S or O atoms; R9 = H, Me); R10 = OH, H, (un)substituted alkyl; R11 = H, Me, CF3] that inhibit Btk, were prepared E.g., a multi-step synthesis of III.CF3CO2H, starting from 4-nitrophenylacetic acid, was given. Exemplified compounds I were tested in the Btk biochem. assay and showed an IC50 of ≤ 2 μM, and certain of exemplified compounds I showed an IC50 of ≤ 1 μM. Pharmaceutical compositions comprising at least one compound 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. Methods for determining the presence of Btk in a sample are described. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).COA of Formula: C5H4Br2N2O

The Article related to pyrazinone amide benzamide preparation btk bruton’s tyrosine kinase inhibitor, antitumor combination chemotherapy btk inhibitor pyrazinone amide benzamide preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.COA of Formula: C5H4Br2N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On March 20, 2008, Whitney, James A.; Di Paolo, Julie; Valleca, Mark A.; Brittelli, David R.; Currie, Kevin S.; Darrow, James W.; Kropf, Jeffrey E.; Lee, Tony; Gallion, Steven L.; Mitchell, Scott A.; Pippen, Douglas A.I.; Blomgren, Peter A.; Stafford, Douglas Gregory published a patent.COA of Formula: C5H4Br2N2O The title of the patent was Preparation of substituted amides as Btk kinase inhibitors. And the patent contained the following:

Methods of inhibiting Btk activity by inhibiting phosphorylation of Y551 of Btk, methods of treating patients by inhibiting Btk activity by inhibiting phosphorylation of Y551 of Btk, chem. entities that bind to Btk and inhibited complexes are provided. Thus, the title compounds I [R = (un)substituted cycloalkyl, aryl, heteroaryl; M = a bond, CH:CH; Q = CR10R11NR12, NR12CR10R11, NR13CO, CONR13, NR14CONR15 (R10, R11 = H, alkyl, haloalkyl; R12-R15 = H, alkyl, haloalkyl, etc.); Z = (un)substituted phenylene, pyridylidene; W = (un)substituted heteroaryl other than imidazo[1,2-a]pyrazine; D = hydrogen bond donor other than H; with the proviso] were prepared E.g., a multi-step synthesis of II, starting from 3,5-dibromo-1H-pyridin-2-one, was given. Exemplified compounds I were tested in the Btk assay and certain of those compounds exhibited an IC50 value less than or equal to 1 μM. Some of the compounds I were tested in the B-cell proliferation assay and exhibited an IC50 value less than or equal to 10 μM. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).COA of Formula: C5H4Br2N2O

The Article related to amide preparation bruton’s tyrosine kinase btk kinase inhibitor, y551 btk phosphorylation inhibitor amide preparation, b cell proliferation inhibitor amide preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.COA of Formula: C5H4Br2N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem