Tag: 200-300

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 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 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 March 8, 2012, Currie, Kevin S.; Wang, Xiaojing; Young, Wendy B. published a patent.Product Details of 87486-34-8 The title of the patent was Preparation of pyridinones and pyrazinones as Btk kinase inhibitors for treating inflammation, immunological disorders, cancer, and other diseases. And the patent contained the following:

Pyridinone and pyrazinone compounds of Formula I (wherein R1 is substituted isoindolinone, thienopyrrolone, or pyrrolothiazolone; R2 is H, Me, or CF3; ring B is ring B is Ph, 5-6 membered heteroaryl, or 8-11 membered heterocyclyl; R3 is H, halo, cyano, etc.; R6 is H, Me, F, etc.; R7 is H, Me F, etc.; R8 is H, Me, CF3, etc.; V is CH or N) including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase are claimed. 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. Synthetic procedures for preparing I are exemplified. Example compound II, prepared in a multistep synthesis that culminated in the cyclization of III, had an IC50 of 0.0364 in a standard biochem. Btk kinase assay. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Product Details of 87486-34-8

The Article related to preparation pyridinone pyrazinone btk kinase inhibitor therapy diagnosis, immune disorder treatment pyridinone pyrazinone btk kinase inhibitor, inflammation cancer treatment pyridinone pyrazinone btk kinase inhibitor and other aspects.Product Details of 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On March 15, 2015, Young, Wendy B.; Barbosa, James; Blomgren, Peter; Bremer, Meire C.; Crawford, James J.; Dambach, Donna; Gallion, Steve; Hymowitz, Sarah G.; Kropf, Jeffrey E.; Lee, Seung H.; Liu, Lichuan; Lubach, Joseph W.; Macaluso, Jen; Maciejewski, Pat; Maurer, Brigitte; Mitchell, Scott A.; Ortwine, Daniel F.; Di Paolo, Julie; Reif, Karin; Scheerens, Heleen; Schmitt, Aaron; Sowell, C. Gregory; Wang, Xiaojing; Wong, Harvey; Xiong, Jin-Ming; Xu, Jianjun; Zhao, Zhongdong; Currie, Kevin S. published an article.Recommanded Product: 87486-34-8 The title of the article was Potent and selective Bruton’s tyrosine kinase inhibitors: Discovery of GDC-0834. And the article contained the following:

SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 resulted in the clin. candidate GDC-0834, which retained the potency and selectivity of CGI-1746, but with much improved PK in preclin. animal models. Structure based design efforts drove this work as modifications to CGI-1746 were investigated at both the solvent exposed region as well as ‘H3 binding pocket’. However, in vitro metabolic evaluation of GDC-0834 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclin. species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclin. efficacy, a single dose IND was filed and GDC-0834 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, GDC-0834 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors. 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 bruton tyrosine kinase inhibitor gdc0834 preparation structure activity pharmacokinetics, amide hydrolysis, bruton’s tyrosine kinase, btk, gdc-0834, kinase inhibitor, rheumatoid arthritis, single dose ind and other aspects.Recommanded Product: 87486-34-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On May 28, 2015, Laurent, Alain; Rose, Yannick published a patent.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone The title of the patent was Preparation of 8-aminoimidazo[3,4-a]pyrazine as Btk protein kinase inhibitors. And the patent contained the following:

The present invention relates to a novel family of protein kinase inhibitors, more specifically the present invention is directed to inhibitors of the members of the Tec and Src protein kinase families. The present invention also relates to processes for the preparation of these compounds [I; X = CH or N; R = H or each (un)substituted alkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; W = OCH2R11 or CH2OR11; R1 = each (un)substituted aryl or heteroaryl; X1, X2 = H or halogen; m, m1 = an integer from O to 4] or pharmaceutically acceptable salts, solvates, solvates of salts, stereoisomers, tautomers, isotopes, prodrugs, complexes or biol. active metabolites thereof, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative, inflammatory, inflammatory and autoimmune diseases, disorders or conditions in which protein kinase activity is implicated. Thus, a solution of intermediate (II) (300 mg), intermediate (III) (397 mg), N,N-dimethylglycine (231 mg), cesium carbonate (1.1 g) and copper(I) iodide (141 mg) in 1,4-dioxane (1.5 mL) was heated in a pressure vessel at 110° overnight and then cooled to room temperature, followed by adding Et acetate, adsorbing the resulting mixture on silica gel, and purification by silica gel chromatog. to give 8-amino-1-(4-phenoxyphenyl)imidazo[3,4-a]pyrazine derivative (IV) as yellow solid. The experimental process involved the reaction of 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone(cas: 936901-72-3).Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

The Article related to aminoimidazopyrazine aminophenoxyphenylimidazopyrazine preparation btk protein kinase inhibitor, proliferative disease inflammatory disease inflammatory autoimmune disease treatment aminoimidazopyrazine and other aspects.Recommanded Product: 3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

On November 10, 2011, Barbosa, Antonio J. M.; Blomgren, Peter A.; Currie, Kevin S.; Krishnamoorthy, Ravi; Kropf, Jeffrey E.; Lee, Seung H.; Mitchell, Scott A.; Ortwine, Daniel; Schmitt, Aaron C.; Wang, Xiaojing; Xu, Jianjun; Young, Wendy; Zhang, Honglu; Zhao, Zhongdong; Zhichkin, Pavel E. published a patent.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one The title of the patent was Preparation of pyridone and azapyridone compounds as Btk inhibitors for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. And the patent contained the following:

The invention is related to the preparation of pyridones and azapyridones I [R1 = H, D, F, CN, OH, etc.; R2-4 = independently alkyl, Cl, NH2, OEt, etc.; R5 = (un)substituted (hetero)aryl, carbocyclyl, etc.; X = (S)0-2, N, NR6, O, CH and derivatives; R6 = H, F, NH2, OH, (un)substituted alkyl; Y, Y’ = independently CR6, N; Z1-4 = independently C, CH and derivatives, N; Z5 = CO, CH2 and derivatives, CH:N and derivatives, NH and derivatives, etc.; one of Z1 and Z2 or X and Z1, where X is not (S)0-2, forms a 5-7 membered aryl, carbocyclyl, heterocyclyl, heteroaryl ring; where alkyl, aryl, carbocyclyl, heterocyclyl, heteroaryl are optionally substituted] their stereoisomers, tautomers, and pharmaceutically acceptable salts useful for inhibiting Btk kinase, and for treating immune disorders, inflammation, cancer, and other Btk-mediated diseases. Methods of using I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathol. conditions, are disclosed. Thus, a multi-step synthesis starting from 5-nitropyrazole-3-carboxylic acid via cyclization of 1-(2-Bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole to 5-Methyl-2-nitro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine and cyclization of Et 1-(2-Aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate to 3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one was given for II. II inhibited Btk kinase (IC50 = 0.002 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 pyridone azapyridone preparation btk inhibitor immune disease inflamation cancer, benzothienopyridinone pyrazinoindolone pyrazinobenzimidazolone methanopyrazinoindolone preparation rheumatoid arthritis and other aspects.Reference of 3,5-Dibromo-1-methylpyrazin-2(1H)-one

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem