pyrazoles-derivatives

On March 17, 2022, Yang, Shengyong; Li, Linli published a patent.Electric Literature of 1187582-58-6 The title of the patent was Preparation of 5-substituted indole-3-amide derivatives for disease treatments targeting RIPK1. And the patent contained the following:

Provided are a 5-substituted indole 3-amide derivative, a preparation method and a use thereof, belonging to the field of medicine. A compound represented by formula I [wherein X1 and X3 = independently N or (un)substituted CH; X2 = (un)substituted NH or CH=CH; R2B = -R2-B; R2 = (un)substituted alkylene,; B = (un)substituted aryl, cycloalkyl, heteroaryl, etc.; R3 = H or (un)substituted alkyl; R4 and R5 = independently H, alkyl, CN, OH, CO2H, etc.; A = (un)substituted aryl or heteroaryl] or a pharmaceutically acceptable salt thereof is provided. For example, II was prepared in a multi-step synthesis. This type of compound can significantly inhibit the activity of RIPK1 kinase, has high selectivity and excellent safety, serves as a RIPK1 kinase inhibitor, and can be used as a potential therapeutic drug for inflammation, immune diseases, tumors and neurodegenerative diseases. TNFα-induced SIRS model experiments proved that the compound can inhibit a RIPK1 kinase in vivo. Pharmacokinetic results showed that this series of compounds has excellent pharmacokinetic properties, thus providing a novel strategy and means for disease treatments targeting RIPK1. The experimental process involved the reaction of 5-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole(cas: 1187582-58-6).Electric Literature of 1187582-58-6

The Article related to preparation indole amide disease treatment ripk1 human, inflammation immune tumor neurodegenerative disease, Heterocyclic Compounds (More Than One Hetero Atom): Other 5-Membered Rings, Two Or More Hetero Atoms and other aspects.Electric Literature of 1187582-58-6

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On March 29, 2012, Bartolozzi, Alessandra; Bosanac, Todd; Chen, Zhidong; De Lombaert, Stephane; Huber, John D.; Liu, Weimin; Lo, Ho Yin; Loke, Pui Leng; Riether, Doris; Tye, Heather; Wu, Lifen; Zindell, Renee M. published a patent.Quality Control of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid The title of the patent was Preparation of oxadiazole inhibitors of leukotriene production. And the patent contained the following:

The title compounds I [R1, R2 = H, alkyl, carboxyxlice (with the proviso that both R1 and R2 are not hydrogen); R3 = (un)substituted 5-11 membered heteroaryl ring containing 1-3 heteroatoms selected from N, O and S; R4 = H, halo, alkyl, nitrile; R5 = (un)substituted alkyl, C3-10 carbocycle, 5-11 membered heterocycle, etc.], useful in treating a leukotriene-mediated disorders, were prepared Thus, reacting compound II (preparation given) with the pyrimidine derivative III afforded the title compound IV. Biol. testing showed that compounds I are effective inhibitors of 5-lipoxygenase activating protein (FLAP) and thus inhibit leukotriene production (IC50 values were given). The invention also relates to pharmaceutical compositions comprising compounds I, methods of I in the treatment of various diseases and disorders, processes for preparing I and intermediates useful in these processes. The experimental process involved the reaction of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid(cas: 1340372-11-3).Quality Control of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

The Article related to oxadiazole preparation leukotriene production ltb4 inhibitor, lipoxygenase activating protein flap inhibitor oxadiazole preparation, Heterocyclic Compounds (More Than One Hetero Atom): Other 5-Membered Rings, Two Or More Hetero Atoms and other aspects.Quality Control of 1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylic acid

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On August 29, 2019, Walters, W. Patrick; Lescarbeau, Andre; Kelley, Elizabeth H.; Shortsleeves, Kelley C.; Taylor, Alexander M.; Pierce, Levi Charles Thomas; Murcko, Mark Andrew; Giordanetto, Fabrizio; Greisman, Jack Benjamin; Maragakis, Paul; Bhat, Sathesh; Konze, Kyle; Dahlgren, Markus Kristofer; Therrien, Eric published a patent.Quality Control of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine The title of the patent was Preparation of heterocyclic compounds as SHP2 phosphatase inhibitors. And the patent contained the following:

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure. Example compound I•formate was prepared by cyclocondensation of tert-Bu (1-(5-amino-1,3,4-thiadiazol-2-yl)-3-methylpiperidin-3-yl)carbamate with 2,3-dichlorobenzaldehyde and 2-isocyano-2,4,4-trimethylpentane followed by deprotection. The invention compounds were evaluated for their SHP2 phosphatase inhibitory activity. From the assay, it was determined that compound I•formate exhibited IC50 value less than 5 μM. The experimental process involved the reaction of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine(cas: 98138-75-1).Quality Control of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine

The Article related to heterocycle preparation shp2 phosphatase inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Quality Control of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On September 26, 2019, Xie, Yinong; Babiss, Lee E. published a patent.Category: pyrazoles-derivatives The title of the patent was Preparation of SHP2 inhibitors and uses thereof. And the patent contained the following:

The invention relates to compounds of formula I and their preparation, useful as inhibitors of protein tyrosine phosphatase SHP2 in the treatment of diseases such as cancer. Compounds of formula I are claimed, in which ring A is (un)substituted aryl, heteroaryl, and bicyclic ring system; X is S, O, NRa, CHRa, S(O), SO2, C(O), or bond; Ra is H and C1-6 hydrocarbyl; ring B is (un)substituted mono-, bi-, tri-, or tetracyclic heterocyclic ring system containing heteroaryl and at least two ring N atoms; and pharmaceutically acceptable salts thereof. Example compound II was prepared via a multistep process with key step of coupling tert-Bu ((1-(5-chloro-4-cyano-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-methylpiperidin-4-yl)methyl)carbamate with 2,3-dichlorophenylboronic acid followed by deprotection. Invention compounds were evaluated for their SHP2 inhibitory activity (data given). The experimental process involved the reaction of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine(cas: 98138-75-1).Category: pyrazoles-derivatives

The Article related to shp2 inhibition treatment cancer, heteroaromatic preparation, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Category: pyrazoles-derivatives

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On July 25, 2019, Blake, James F.; Dai, Donghua; Haas, Julia; Jiang, Yutong; Kolakowski, Gabrielle R.; Metcalf, Andrew T.; Moreno, David A.; Prigaro, Brett; Ren, Li published a patent.Recommanded Product: 1028092-65-0 The title of the patent was Preparation of substituted pyrazolo[3,4-d]pyrimidine compounds as RET kinase inhibitors. And the patent contained the following:

The invention is related to the preparation of compounds I [R1 = (un)substituted 5-membered heteroaryl ring having 2-3 ring heteroatoms independently selected from N, O and S, provided that when R1 is an isoxazolyl ring, then R1 is substituted with 2 specified substituents; R2 = H, alkyl, cyanoalkyl, etc.], their tautomers, stereoisomers, pharmaceutically acceptable salts and solvates, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase. Thus, II was prepared in 5 steps from 5-cyclopropylisoxazole-3-carboxylic acid and malononitrile using isopropylhydrazine hydrochloride, formamide, NBS and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. I were screened for their ability to inhibit several RET kinase forms (wild type, V804M M918T, G810R, and G810S mutants) (data given for representative compounds I in an enzyme assay and/or cell assay). Pharmaceutical compositions comprising compound I, alone or in combination with an addnl. therapy or therapeutic agent, were disclosed. The experimental process involved the reaction of 3-Phenyl-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 1028092-65-0).Recommanded Product: 1028092-65-0

The Article related to pyrazolopyrimidine preparation ret kinase inhibitor antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Recommanded Product: 1028092-65-0

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On April 1, 2021, Xie, Yinong; Babiss, Lee E. published a patent.SDS of cas: 98138-75-1 The title of the patent was Preparation of SHP2 inhibitors for treatment of cancer. And the patent contained the following:

Disclosed are compounds of formula I, useful as inhibitors of protein tyrosine phosphatase SHP2 for the treatment of cancer. Compounds of formula I [wherein X = S; Ring A = (un)substituted aryl having 6-10 carbons, (un)substituted 5- to 6-membered mono-cyclic heteroaryl, or (un)substituted bicyclic ring system having 5-10 ring carbons; RA and RB independently = H or C1-12 hydrocarbyl, or N(RA)(RB) optionally = substituted heterocyclic ring system] or pharmaceutically acceptable salts thereof, are claimed and exemplified. Thus, disubstituted 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one II was prepared from a multistep synthesis (preparation given). Exemplified I were evaluated for inhibition of SHP2 from which II demonstrated an IC50 = ≤ 50 nM. The pharmaceutical compositions comprising compounds of Formula I, methods of synthesis of these compounds, methods of treatment for diseases associated with the aberrant activity of SHP2 such as cancer using these compounds or compositions containing these compounds are also disclosed. The experimental process involved the reaction of 6-Chloro-4-methoxy-1H-pyrazolo[3,4-d]pyrimidine(cas: 98138-75-1).SDS of cas: 98138-75-1

The Article related to dihydropyrazolopyrimidinone preparation shp2 inhibitor preparation inhibitor cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.SDS of cas: 98138-75-1

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On April 30, 2009, Barlaam, Bernard Christophe; Bower, Justin Fairfield; Delouvrie, Benedicte; Fairley, Gary; Harris, Craig Steven; Lambert, Christine; Ouvry, Gilles; Winter, Jon James Gordon published a patent.Category: pyrazoles-derivatives The title of the patent was Pyridine and pyrazine derivatives as Axl and/or c-Met receptor enzyme inhibitors and their preparation, pharmaceutical compositions and use in the treatment of tumors. And the patent contained the following:

The invention concerns pyridine a nd pyrazine derivatives of formula I or a pharmaceutically-acceptable salt thereof, processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of tumors. Compounds of formula I wherein W is CH and N; J is O and S; each G1, G2, G3 and G4 is CH and N, proved that no more than two of G1,G2, G3 and R4 is N; A is (un)substituted Ph, (un)substituted 5- to 6-membered monocyclic heteroaryl; and (un)substituted 8- to 10-membered bicyclic ring; each R3 is independently H, halo, CN, amino, sulfamoyl, CF3, C1-8 alkyl, etc.; n is 0, 1, 2, and 3; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by cyclization of 2-aminophenol with 2-amino-5-bromopyridine-3-carboxylic acid; the resulting 3-(benzoxazol-2-yl)-5-bromopyridin-2-amine underwent cross-coupling with 4-(dimethylaminomethyl)phenylboronic acid to give compound II. All the invention compounds were evaluated for their Axl and c-Met receptor tyrosine kinase inhibitory activity. From the Axl tyrosine kinase assay, it was determined that compound II exhibited 99.8 % inhibition at 1 μM concentration The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Category: pyrazoles-derivatives

The Article related to pyridine preparation axl cmet tyrosine kinase inhibitor treatment tumor, pyrazine preparation axl cmet tyrosine kinase inhibitor treatment tumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Category: pyrazoles-derivatives

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On July 29, 2022, Perma Tenzin, Puno; Sun, Handong; Zhou, Yuanfei; Yan, Bingchao; Yang, Qian; Du, Xue; Hu, Kun published a patent.Related Products of 1014631-89-0 The title of the patent was Preparation of ent-kauranoid derivatives as antitumor drugs. And the patent contained the following:

The invention discloses a preparation of ent-kauranoid derivatives I [wherein R=(un)substituted C3-C8 alkyl and cycloalkyl, heterocyclic group containing N, O, S, substituted Ph, etc.] as antitumor drugs, which has the advantages of easy availability of raw materials, high yield and good anti-tumor effect. For example, (3aS,5aR,6S,7aR,10S,12aS,12bR,13R)-6-hydroxy-5,5-dimethyl-9-methylene-3,7,8-trioxododecahydro-1H,3H-7a,10-methanocyclohepta[6,7]indeno[1,7a-c]furan-13-yl butyrate was prepared by the following steps: oxidation of oridonin; selective reduction; diazotization; oxidation; rearrangement reaction; cyclization to obtain calyx lactone B; esterification. The title compound is used to prepare anti-tumor drugs, and tumors include cervical cancer, colon cancer, ovarian cancer, lung cancer, prostate cancer, breast cancer and liver cancer. The experimental process involved the reaction of 1-(Pyridin-3-yl)-1H-pyrazole-4-carboxylic acid(cas: 1014631-89-0).Related Products of 1014631-89-0

The Article related to preparation ent kauranoid antitumor oxidation reduction diazotization cyclization esterification, Terpenes and Terpenoids: Diterpenes (C20), Including Gibberellins, Retinoids, Quassinoids, and Tocopherols and other aspects.Related Products of 1014631-89-0

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Kikalishvili, T. Dzh.; Kereselidze, Dzh. A. published an article in 2002, the title of the article was Quantum-chemical study of some physico-chemical properties of derivatives of pyrazole.COA of Formula: C4H6N2O And the article contains the following content:

By modern semiempirical quantum-chem. method the charges on the atoms, dipole moments, and ionization potentials of derivatives of pyrazole were calculated and the correlation anal. using Taft’s substituent constants was carried out. The possibility of quant. description of reactivity of pyrazoles was shown. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).COA of Formula: C4H6N2O

The Article related to pyrazole derivative structure property reactivity, Physical Organic Chemistry: Theoretical Organic Chemical Concepts, Including Quantum and Molecular Mechanical Studies and other aspects.COA of Formula: C4H6N2O

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

On September 23, 2021, Holson, Edward; Blum, Charles published a patent.Electric Literature of 1014631-89-0 The title of the patent was Preparation of benzenesulfonamide derivatives as TRAP1 modulators and uses thereof. And the patent contained the following:

The disclosure provides compounds of formula I and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor (“”TNF””) receptor associated protein 1 (“”TRAP1″”) modulators (e.g., TRAP1 activators). The provided compounds of formula I may also rescue the activity in PTEN-induced kinase 1 (“”PINK1″”) loss of function contexts. The provided compounds of formula I may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds of formula I may also refold or solubilize aggregated or misfolded proteins such as α-synuclein. The disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof). Compounds of formula I wherein A and E are independently aryl and heteroaryl; dashed bonds are single and double bonds are valency permits; m is 0, 1 and 2; n and p are independently 0 – 13; each R1 is independently halo, (un)substituted alkyl, (un)substituted alkenyl, (un)substituted alkynyl, etc.; R3 and R6 are independently H, (un)substituted alkyl and nitrogen protecting group; R1R3 may be taken together to form (un)substituted heterocyclyl; each R4 is independently halo, (un)substituted alkyl, (un)substituted alkenyl, (un)substituted aryl, etc.; R5 and R9 are independently H, halo, (un)substituted alkyl, (un)substituted alkenyl, (un)substituted alkynyl, etc.; each R7 is independently (un)substituted alkyl, (un)substituted alkenyl, (un)substituted alkynyl, (un)substituted aryl, etc.; and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof, are claimed. Example compound II was prepared by amidation of oxazole-5-carboxylic acid with 5-amino-N-(4-bromophenyl)-2-methoxybenzenesulfonamide. The invention compounds were evaluated for their TRAP1 modulatory activity. From the assay, it was determined that compound II exhibited an EC50 value in the range of 20μM to 100μM and an Emax value in the range of 160 – 199%. The experimental process involved the reaction of 1-(Pyridin-3-yl)-1H-pyrazole-4-carboxylic acid(cas: 1014631-89-0).Electric Literature of 1014631-89-0

The Article related to benzenesulfonamide preparation trap1 modulator, Benzene, Its Derivatives, and Condensed Benzenoid Compounds: Amides, Amidines, Imidic Esters, Hydrazides, and Hydrazonic Esters and other aspects.Electric Literature of 1014631-89-0

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics