Tag: 200-300

Ennis, Michael D. published an article in 2012, the title of the article was Oxalyl bromide.Name: 3,5-Dibromo-1-methylpyrazin-2(1H)-one And the article contains the following content:

Synthesis, properties, availability, handling and applications of oxalyl bromide as a reactive acid halide and in heterocycle synthesis was reviewed. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Name: 3,5-Dibromo-1-methylpyrazin-2(1H)-one

The Article related to review oxalyl bromide bromination heterocycle preparation safety, Aliphatic Compounds: Reviews and other aspects.Name: 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On August 13, 2020, Crawford, James J.; Lee, Wendy; Johnson, Adam R.; Delatorre, Kelly J.; Chen, Jacob; Eigenbrot, Charles; Heidmann, Julia; Kakiuchi-Kiyota, Satoko; Katewa, Arna; Kiefer, James R.; Liu, Lichuan; Lubach, Joseph W.; Misner, Dinah; Purkey, Hans; Reif, Karin; Vogt, Jennifer; Wong, Harvey; Yu, Christine; Young, Wendy B. published an article.Synthetic Route of 87486-34-8 The title of the article was Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity. And the article contained the following:

Bruton’s tyrosine kinase (Btk) is thought to play a pathogenic role in chronic immune diseases such as rheumatoid arthritis and lupus. While covalent, irreversible Btk inhibitors are approved for treatment of hematol. malignancies, they are not approved for autoimmune indications. In efforts to develop addnl. series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clin. stage inhibitor fenebrutinib using cyclopropyl amide isosteres of the 2-aminopyridyl group to occupy the flat, lipophilic H2 pocket. While drug-like properties were retained – and in some cases improved – a safety liability in the form of hERG inhibition was observed When a fluorocyclopropyl amide was incorporated, Btk and off-target activity was found to be stereodependent and a lead compound was identified in the form of the (R,R) stereoisomer. 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 fluorocyclopropyl amide btk inhibitor stereochem herg inhibition, Alicyclic Compounds: Cyclopropanes and other aspects.Synthetic Route of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On July 11, 2013, Jin, Meizhong; Petronella, Brenda A.; Cooke, Andy; Kadalbajoo, Mridula; Siu, Kam W.; Kleinberg, Andrew; May, Earl W.; Gokhale, Prafulla C.; Schulz, Ryan; Kahler, Jennifer; Bittner, Mark A.; Foreman, Kenneth; Pachter, Jonathan A.; Wild, Robert; Epstein, David; Mulvihill, Mark J. published an article.Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the article was Discovery of Novel Insulin-Like Growth Factor-1 Receptor Inhibitors with Unique Time-Dependent Binding Kinetics. And the article contained the following:

This letter describes a series of small mol. inhibitors of IGF-1R with unique time-dependent binding kinetics and slow off-rates. Structure-activity and structure-kinetic relationships were elucidated and guided further optimizations within the series, culminating in compound 2. With an IGF-1R dissociative half-life (t1/2) of >100 h, compound 2 demonstrated significant and extended PD effects in conjunction with tumor growth inhibition in xenograft models at a remarkably low and intermittent dose, which correlated with the observed in vitro slow off-rate properties. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to preparation igf1 receptor inhibitor binding kinetics structure, insulin-like growth factor-1 receptor (igf-1r), cancer, slow off-rate, time-dependent inhibition, Pharmacology: Structure-Activity and other aspects.Application In Synthesis of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 30, 2013, Sawa, Tadaki; Kawabata, Wataru; Asami, Saiko published a patent.HPLC of Formula: 87486-34-8 The title of the patent was Novel fluorescent probe, and kinase inhibitor novel screening method. And the patent contained the following:

A novel benzoxadiazole fluorescent probe shown by the formula (I) is provided, which enables to screen a kinase inhibitor. In (I), Z represents a compound possessing a kinase inhibitory activity; L represents an optionally bound or substituted amino group, a carbonyl group, an optionally substituted hydrocarbon group, an optionally substituted alkylcarbamoyl group, an optionally substituted acylamino group, a sulfide group, or an optionally substituted alkoxy group; X represents an optionally bound or substituted amino group, an optionally substituted hydrazino group, or a thiocarbonyl amino group; and R1 represents a nitro group, or a dimethylsulfamoyl group. 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 benzoxadiazole fluorescent probe kinase inhibitor screening, Biochemical Methods: Spectral and Related Methods and other aspects.HPLC of Formula: 87486-34-8

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