Category: 1186608-73-0

On September 20, 2018, Bandiera, Tiziano; Bertozzi, Fabio; Di Fruscia, Paolo; Sorana, Federico; Berti, Francesco; Rodriguez Gimeno, Alejandra; Caci, Emanuela; Ferrera, Loretta; Pedemonte, Nicoletta; Vicente Galietta, Luis Juan published a patent.Category: pyrazoles-derivatives The title of the patent was Preparation of heterocyclic compounds for the treatment of cystic fibrosis. And the patent contained the following:

The invention relates to compounds of formula I or pharmaceutically acceptable salts or solvates thereof; their preparation an use to modulate CFTR protein or ABC protein activities. Compounds of formula I, wherein R1 is C1-6 alkyl, C3-6 cycloalkyl and hydroxy-C1-6 alkyl; Z is CO and SO2; X1, X2, X3 and X4 are independently CR and N; R is H, C1-6 alkyl, aryl, etc.; R2 is H, C1-6 alkyl, OH, CN, etc.; A1 , A2, A3 and A4 are independently O, CO, SO2, etc.; B is (un)substituted aromatic and heteroaromatic; n and m are independently 0, 1, 2; and pharmaceutically acceptable salts and solvates thereof, are claimed. Example compound II was prepared by cyclocondensation of 3-hydrazinobenzoic acid tert-Bu 4-oxo-3-(2,2,2-trifluoroacetyl)piperidine-1-carboxylate to give 3-[5-tert-butoxycarbonyl-3-(trifluoromethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl]benzoic acid, which underwent amidation with N-methyl-1,3-benzodioxol-5-amine hydrochloride to give II. The invention compounds were evaluated for their CFTR modulatory activity. From the assay, it was determined that compound II exhibited EC50 value of < 1 μM. The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).Category: pyrazoles-derivatives

The Article related to heterocycle preparation cystic fibrosis cftr abc protein modulator, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Category: pyrazoles-derivatives

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

On November 26, 2020, Bandiera, Tiziano; Bertozzi, Fabio; Di Fruscia, Paolo; Sorana, Federico; Berti, Francesco; Rodriguez Gimeno, Alejandra; Caci, Emanuela; Ferrera, Loretta; Pedemonte, Nicoletta; Vicente Galietta, Luis Juan published a patent.Synthetic Route of 1186608-73-0 The title of the patent was Preparation of pyrazolopyridines and related heterocycles and compositions containing them for the treatment of cystic fibrosis. And the patent contained the following:

The invention relates to preparation of pyrazolopyridines and related heterocycles of formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds I and their uses, in particular to modulate CFTR protein or ABC protein activities. Compounds I wherein R1 is H; Z is CO or SO2; X1-X4 each independently is CRVII and N, with the proviso that the number of nitrogen atoms in the ring is comprised from O to 2; R2 is H, OH, NO, etc.; A1-A4 each independently is O, SO2, CO, etc.; B represents an unsubstituted or a substituted aromatic or heteroaromatic ring; n and m are each independently selected from the group consisting of O, 1, 2; etc., are claimed. The example compound II was prepared using 3-hydrazinobenzoic acid as starting material (procedure given). Compounds I were evaluated for their biol. activity (data given). Compounds I and pharmaceutical composition comprising them, are modulators of CFTR protein or ABC protein activities, and can be used in treatment of cystic fibrosis and other diseases. The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).Synthetic Route of 1186608-73-0

The Article related to pyrazolopyridine preparation cftr modulator abc protein cystic fibrosis treatment, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Synthetic Route of 1186608-73-0

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

On September 11, 2009, Ahrendt, Kateri A.; Buckmelter, Alexandre J.; De Meese, Jason; Grina, Jonas; Hansen, Joshua D.; Laird, Ellen R.; Lunghofer, Paul; Moreno, David; Newhouse, Brad; Ren, Li; Seo, Jeongbeob; Tian, Hongqi; Wenglowsky, Steven Mark; Feng, Bainian; Gunzner, Janet; Malesky, Kim; Mathieu, Simon; Rudolph, Joachim; Wen, Zhaoyang; Young, Wendy B. published a patent.Reference of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine The title of the patent was N-Pyrazolo[3,4-b]pyridinyl benzamide derivatives as Raf inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. And the patent contained the following:

Compounds of formula I are useful for inhibition of Raf kinases. Methods of using compounds of formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo prevention or treatment of Raf-mediated disorders in mammalian cells, or associated pathol. conditions are disclosed. Compounds of formula I wherein R1 and R2 are independently H, halo, CN, C1-3 alkyl and C1-3 alkoxy; R3 is H, halo and C1-3 alkyl; R4 is C3-5 cycloalkyl, C1-6 alkyl, C2-6 alkenyl, etc.; R5 is H, halo, CN, NH2 and derivatives, etc.; and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by cyclization of 1H-pyrazol-5-amine with 2-bromomalonaldehyde; the resulting 5-bromo-1H-pyrazolo[3,4-b]pyridine underwent alkylation with 2-(trimethylsilyl)ethoxymethyl chloride to give 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine, which underwent cross-coupling with tert-Bu carbamate to give tert-Bu 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-ylcarbamate, which underwent hydrolysis to give 1H-pyrazolo[3,4-b]pyridin-5-amine, which underwent amidation with 2.6-difluoro-3-(propylsulfonamido)benzoic acid to give compound II. All the invention compounds were evaluated for their Raf inhibitory activity. From the assay, it was determined that compound II along with the other example compound exhibited IC50 values of less than 1 μM. The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).Reference of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine

The Article related to pyrazolopyridinyl benzamide preparation raf inhibitor treatment disease, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Reference of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine

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

On October 4, 2012, Vankayalapati, Hariprasad; Appalaneni, Rajendra P.; Reddy, Y. Venkata Krishna published a patent.COA of Formula: C7H8N4 The title of the patent was Preparation of substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine and pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors. And the patent contained the following:

This invention relates to the title compounds I-III [X = N, CH; L1 = a bond, (un)substituted 6-membered aryl, heteroaryl, etc.; R1-R3 = H, halo, CN, etc.; Q = NH, O, S, etc.; L2 = IV (wherein X1 = N, CH; X2 = N, CH; X3 = N, CH; R10 = H, halo, CN, etc.)] which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson’s disease, Alzheimer’s disease, Down’s syndrome, Huntington’s disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases, and to methods for making them. Seventy title compounds were prepared and formulated. For example, a multi-step synthesis of V, starting from mucobromic acid, was described. Exemplified title compounds were tested in the LRRK2 kinase assay (data given). Also disclosed are pharmaceutical compositions including the title compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using title compounds and pharmaceutical compositions including the title compounds The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).COA of Formula: C7H8N4

The Article related to pyrazinylpyrazolopyridine pyrazolopyridine preparation protein kinase inhibitor antitumor antiinflammatory antiparkinsonian, parkinson’s alzheimer’s disease down’s syndrome treatment pyrazinylpyrazolopyridine pyrazolopyridine preparation, huntington’s disease neurodegenerative cns disorder treatment pyrazinylpyrazolopyridine pyrazolopyridine preparation and other aspects.COA of Formula: C7H8N4

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

On May 31, 2011, Wenglowsky, Steve; Ren, Li; Ahrendt, Kateri A.; Laird, Ellen R.; Aliagas, Ignacio; Alicke, Bruno; Buckmelter, Alex J.; Choo, Edna F.; Dinkel, Victoria; Feng, Bainian; Gloor, Susan L.; Gould, Stephen E.; Gross, Stefan; Gunzner-Toste, Janet; Hansen, Joshua D.; Hatzivassiliou, Georgia; Liu, Bonnie; Malesky, Kim; Mathieu, Simon; Newhouse, Brad; Raddatz, Nicholas J.; Ran, Yingqing; Rana, Sumeet; Randolph, Nikole; Risom, Tyler; Rudolph, Joachim; Savage, Scott; Selby, LeAnn T.; Shrag, Michael; Song, Kyung; Sturgis, Hillary L.; Voegtli, Walter C.; Wen, Zhaoyang; Willis, Brandon S.; Woessner, Richard D.; Wu, Wen-I.; Young, Wendy B.; Grina, Jonas published an article.Computed Properties of 1186608-73-0 The title of the article was Pyrazolopyridine Inhibitors of B-RafV600E. Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors. And the article contained the following:

The V600E mutation of B-Raf kinase results in constitutive activation of the MAPK signaling pathway and is present in approx. 7% of all cancers. Using structure-based design, a novel series of pyrazolopyridine inhibitors of B-RafV600E was developed. Optimization led to the identification of 3-methoxy pyrazolopyridines 17 and 19, potent, selective, and orally bioavailable agents that inhibited tumor growth in a mouse xenograft model driven by B-RafV600E with no effect on body weight On the basis of their in vivo efficacy and preliminary safety profiles, 17 and 19 were selected for further preclin. evaluation. The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).Computed Properties of 1186608-73-0

The Article related to pyrazolopyridine derivative braf kinase inhibitor preparation antitumor pharmacokinetics toxicity, b-rafv600e, mapk pathway, amorphous spray-dried dispersion, pyrazolopyridine, targeted therapy and other aspects.Computed Properties of 1186608-73-0

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