23000-43-3

Usage

Uses

Used in Pharmaceutical Industry:
4-CHLORO-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE is used as a key intermediate in the synthesis of potential drugs for the treatment of various diseases. Its unique structure and biological activities make it a valuable component in the development of therapeutic agents.
Used in Cancer Treatment:
In the field of oncology, 4-CHLORO-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE is used as a precursor in the development of anticancer drugs. Its chemical properties allow for the creation of molecules that can target and inhibit the growth of cancer cells, offering a potential treatment option for patients suffering from various types of cancer.
Used in Inflammation Management:
4-CHLORO-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE is also utilized in the synthesis of compounds that can help manage inflammation. Its ability to modulate immune responses and reduce inflammation makes it a useful component in the development of anti-inflammatory drugs.
Used in Infectious Disease Treatment:
In the realm of infectious diseases, 4-CHLORO-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE serves as a building block for the synthesis of compounds with potential antimicrobial and antiviral properties. Its unique structure allows for the development of drugs that can target and combat various pathogens, offering new treatment options for infectious diseases.
Used as a Building Block in Chemical Synthesis:
Beyond its direct applications in drug development, 4-CHLORO-1-METHYL-1H-PYRAZOLO[3,4-D]PYRIMIDINE is also used as a versatile building block in the synthesis of different chemical compounds with potential biological activities. Its presence in various molecular structures can lead to the discovery of new compounds with therapeutic or diagnostic applications.

InChI:InChI=1/C6H5ClN4/c1-11-6-4(2-10-11)5(7)8-3-9-6/h2-3H,1H3

Upstream product

• 5399-92-8 4-chloro-1H-pyrazolo[3,4-d]pyrimidine 
• 74-88-4 methyl iodide 

Downstream Products

• 5334-53-2 4-methoxy-1-methyl-1H-pyrazolo-<3,4-d>pyrimidine 
• 100319-01-5 cyclohexyl-(1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-amine 
• 105945-90-2 (1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-p-tolyl-amine 
• 5334-71-4 2-(1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-ethanol 
• 100124-64-9 4-(4-chloro-phenylsulfanyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidine 
• 100136-96-7 1-methyl-4-phenoxy-1H-pyrazolo[3,4-d]pyrimidine 
• 6288-86-4 1H-pyrazolo<3,4-d>pyrimidin-4(5H)-one 
• 5334-99-6 4-amino-1-methyl-1H-pyrazolo<3,4-d>pyrimidine 
• 5334-72-5 4-hydrazino-1-methyl-1H-pyrazolo[3,4-d]pyrimidine 
• 130235-73-3 4-(3-chlorobenzyloxy)-1-methyl-1H-pyrazolo<3.4-d>pyrimidine 
• 130235-72-2 4-(2-chlorobenzyloxy)-1-methyl-1H-pyrazolo<3.4-d>pyrimidine 
• 130235-62-0 (4-Fluoro-phenyl)-(1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-methanone 
• 59564-10-2 (4-chloro-phenyl)-(1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-methanone 
• 130235-75-5 4-(4-chlorophenyl)-1-methyl-1H-pyrazolo<3.4-d>pyrimidine 

Relevant academic research and scientific papers

Palladium-catalyzed regioselective direct C–H arylation of?pyrazolo[3,4-d]pyrimidines

Nitrogenous bicycles are an apparently endless field of organic and biological research. In this study, we disclose an efficient pathway to the synthesis of the pyrazolo[3,4-d]pyrimidine scaffold in three steps from allopurinol. This key intermediate was engaged in the first example of regioselective C–H arylation catalyzed by palladium to access a library of 3-substituted-1-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines.

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of 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.

ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP-1) INHIBITORS AND USES THEREOF

Disclosed herein are methods and compounds of augmenting and enhancing the production of type I IFNs in vivo. In some embodiments, the compounds disclosed herein are ENPP-1 inhibitors, pharmaceutical compositions, and methods for the treatment of cancer or a viral infection.

Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4- d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds

Alkylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-methyl product 4-methoxy-2-methyl-2H-pyrazolo[3,4-d]pyrimidine (3b) in an 8/1 ratio over N1-methyl product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined the molecular weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO.

Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors

Aiming to explore novel BRAFV600E and VEGFR-2 dual inhibitors, a series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and biologically evaluated in this study. Most of the synthesized 1H-pyrazolo[3,4-d]pyrimidine compounds displayed moderate to high potent activity in both enzymatic and cellular proliferation assays. Among these compounds, 9e, 9g, 9m and 9u showed remarkably high inhibitory activities against both BRAFV600E and VEGFR-2 kinase comparable to positive control Sorafenib. Particularly, compound 9u also showed potent anti-proliferative activity against BRAFV600E-expressing A375 (IC50 = 1.74 μM) and H-29 (IC50 = 6.92 μM) as well as VEGFR-2-expressing HUVEC (IC50 = 5.89 μM), which was also comparable to Sorafenib. Furthermore, kinase selectivity profile showed that 9u had almost poor or no significant inhibitory activity against wild-type BRAF and 15 other tested protein kinases. Flow cytometric analysis showed that compound 9u mainly arrested the A375 and HUVEC cell lines in the G0/G1 stage with a concentration-dependent effect. In addition, the molecular docking and molecular dynamics simulations suggested that 9u adopted a similar binding pattern with Sorafenib at the ATP-binding sites of BRAFV600E and VEGFR-2. Taken together, these results indicated that compound 9u may serve as novel lead compound in research on more effective BRAFV600E and VEGFR-2 dual inhibitors.

Bisarylureas based on 1H-Pyrazolo[3,4-d]pyrimidine Scaffold as Novel Pan-RAF inhibitors with potent anti-proliferative activities: Structure-based design, synthesis, biological evaluation & molecular modelling studies

RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAFV600E kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK). The most promising compound, 1v, exhibited potent inhibitory activity against not only BRAFV600E (half maximal inhibitory concentration, IC50 = 23.6 nM) but also wild-Type BRAF (IC50 = 51.5 nM) and C-RAF (IC50 = 8.5 nM), and effective cellular anti-proliferative activities against A375, HT-29, PC-3 and A549 cell lines as well as a very good selectivity profile. Moreover, compound 1v mainly arrested the A375 cell line in the G0/G1 stage, and showed significant suppression of MEK (mitogen-Activated protein kinase kinase) phosphorylation in A375 and HT-29 cell lines. Taken together, the optimal compound 1v showed excellent in vitro potency as a pan-RAF inhibitor. In addition, the promise of compound 1v was further confirmed by molecular dynamics simulation and binding free energy calculations.

1H-pyrazolo[3,4-d]pyrimidin compound and preparation method and application thereof

The invention discloses a 1H-pyrazolo[3,4-d]pyrimidin compound and a preparation method and application thereof. The 1H-pyrazolo[3,4-d]pyrimidin compound has the structural formula as shown in the description. Meanwhile, the invention discloses the preparation method of the 1H-pyrazolo[3,4-d]pyrimidin compound and application of the 1H-pyrazolo[3,4-d]pyrimidin compound to preparation of medicines for treating protein kinase activity abnormity related diseases. The invention provides the 1H-pyrazolo[3,4-d]pyrimidin compound which is novel in structure and has remarkable anti-tumor activities, and the 1H-pyrazolo[3,4-d]pyrimidin compound can serve as a double-target inhibitor of BRAF/VEGFR-2 kinase and has a favorable effect and a wide application prospect in the aspect of treating diseases caused by protein kinase activity abnormity.

Substituted pyrazolopyrimidines

The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions that include substituted heterobicyclic pyrimidines of Formula (I): wherein R1, R2, R3, R4, R5, X, W, and ring A are as defined herein; pharmaceutical compositions of substituted heterobicyclic pyrimidines of Formula (I); and their use in the treatment of chronic neurodegenerative diseases, neurotraumatic diseases, depression and/or diabetes. More particularly, the present invention relates to substituted pyrazolopyrimidines of Formula (I).