50427-77-5

Usage

Chemical Properties

Off-White Solid

Uses

5-AMino-1-phenylpyrazole-4-carboxamide is used as a heterocyclic scaffold.

InChI:InChI=1/C10H10N4O/c11-9-8(10(12)15)6-13-14(9)7-4-2-1-3-5-7/h1-6H,11H2,(H2,12,15)

Upstream product

• 5334-43-0 5-Amino-4-cyano-1-phenylpyrazole 
• 16078-71-0 ethyl 5-amino-1-phenyl-1H-pyrazole-4-carboxylate 
• 100-63-0 phenylhydrazine 
• 59-88-1 phenylhydrazine hydrochloride 

Downstream Products

• 51649-70-8 6-methyl-1-phenyl-1H-pyrazolo<3,4-d><1,3>oxazin-4(3H)-one 
• 15973-83-8 4,6-Dioxo-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo<3,4-d>pyrimidine 
• 130925-67-6 1,6‐diphenyl‐1,5‐dihydro‐4H‐pyrazolo[3,4‐d]pyrimidin‐4‐one 
• 21314-17-0 1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 5394-42-3 6-ethyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 139954-47-5 6-(2,4-Dichloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 
• 139954-45-3 6-(4-chlorophenyl)-1-phenyl-1,5-dihydro-4Hpyrazolo[3,4-d]pyrimidin-4-one 
• 139954-46-4 6-(4-Nitro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 
• 91974-63-9 6-methyl-1-phenyl-1H-pyrazolo<3,4-d>pyrimidine-4(5H)-one 
• 130925-64-3 1-phenyl-6-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 139954-44-2 1-phenyl-6-(p-tolyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 139954-43-1 6-(4-methoxyphenyl)-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 94331-62-1 6-benzyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 
• 136010-89-4 5-(3-benzoylthioureido)-1-phenylpyrazole-4-carboxamide 

Relevant academic research and scientific papers

The new green procedure for pyrazolopyrimidinone based dihydropyrimidinones and their antibacterial screening

A series of novel hybrid aza heterocycles containing pyrazolopyrimidinone and dihydropyrimidinone scaffolds was developed using Cu(II) catalyzed Biginelli condensation as an efficient, new green synthetic method under mild and solvent free conditions. Pyr

Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors

A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f

Design, synthesis and anticancer evaluation of 1H-pyrazolo[3,4-d]pyrimidine derivatives as potent EGFRWT and EGFRT790M inhibitors and apoptosis inducers

In our attempt to develop effective EGFR-TKIs, two series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized. All the newly synthesized compounds were evaluated in vitro for their inhibitory activities against EGFRWT. Compounds 15b, 15j, and 18d potently inhibited EGFRWT at sub-micro molar IC50 values comparable to that of erlotinib. Moreover, thirteen compounds that showed promising IC50 values against EGFRWT were tested in vitro for their inhibitory activities against mutant EGFRT790M. Compounds 17d and 17f exhibited potent inhibitory activities towards EGFRT790M comparable to osimertinib. Compounds that showed promising IC50 values against EGFRWT were further tested for their anti-proliferative activities against three cancer cell lines bearing EGFRWT (MCF-7, HepG2, A549), and two cancer cell lines bearing EGFRT790M (H1975 and HCC827). Compounds 15g, 15j, 15n, 18d and 18e were the most potent anticancer agents against the EGFRWT containing cells, while compounds 15e, 17d and 17f showed promising anti-proliferative activities against EGFRT790M containing cells. Furthermore, the most active compound 18d was selected for further studies regarding to its effects on cell cycle progression and induction of apoptosis in the HepG2 cell line. The results indicated that this compound is good apoptotic agent and arrests G0/G1and G2/M phases of cell cycle. Finally, molecular docking studies were performed to investigate binding pattern of the synthesized compounds with the prospective targets, EGFRWT (PDB: 4HJO) and EGFRT790M (PDB: 3W2O).

Synthesis of pyrazole-carboxamides and pyrazole-carboxylic acids derivatives: Simple methods to access powerful building blocks

Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.

COMBINATION THERAPY FOR TREATING MPS1

The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.

Pharmacophore-linked pyrazolo[3,4-d]pyrimidines as EGFR-TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies

Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4-d]pyrimidine is a versatile scaffold that has been exploited for developing potential anticancer agents. On the basis of fragment-based drug discovery, considering the essential pharmacophoric features of potent EGFR tyrosine kinase (TK) inhibitors, herein, we report the design and synthesis of new hybrid molecules of the pyrazolo[3,4-d]pyrimidine scaffold linked with diverse pharmacophoric fragments with reported anticancer potential. These fragments include hydrazone, indoline-2-one, phthalimide, thiourea, oxadiazole, pyrazole, and dihydropyrazole. The synthesized molecules were evaluated for their anticancer activity against the human breast cancer cell line, MCF-7. The obtained results revealed comparable antitumor activity with that of the reference drugs doxorubicin and toceranib. Docking studies were performed along with EGFR-TK and ADMET profiling studies. The results of the docking studies showed the ability of the designed compounds to interact with key residues of the EGFR-TK through a number of covalent and noncovalent interactions. The obtained activity of compound 25 (IC50 = 2.89 μM) suggested that it may serve as a lead for further optimization and drug development.

Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells

The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.

Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy

PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1H NMR, 13C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI50 level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC50 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC50 of 5.827 ± 0.46 μM, but significantly inhibited the Wnt/β-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.

Regiocontrolled synthesis of 3- and 5-aminopyrazoles, pyrazolo[3,4-d] pyrimidines, pyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]quinolinones as MAPK inhibitors

Microwave irradiation of a hydrazine and 3-methoxyacrylonitrile, ethoxymethylenemalononitrile or ethyl acetoacetate provides rapid access to 3- or 5-substituted pyrazoles in excellent yield and with total regiocontrol in a process that can be switched from one regioisomer to the other by choice of conditions. Subsequent reaction, either by microwave-assisted hydrolysis and cyclocondensation with formamide, Hantzsch-type three-component reaction with an aldehyde and ketone, or by cyclocondensation with 2-nitrobenzaldehyde, provides the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-b]pyridine or pyrazolo[3,4-b] quinolin-4-one framework, respectively, of inhibitors of mitogen-activated protein kinases.

Synthesis of novel 2-alkyl-4-substituted-amino-pyrazolo[3,4-d]pyrimidines as new leads for anti-bacterial and anti-cancer activity

Treatment of 6-alkyl-1-phenyl-4-chloro-(1H)-pyrazolo[3,4-d]pyrimidines, with different amines afforded a series of compounds whose identity and purity were confirmed by spectral and analytical means. The compounds were tested for antibacterial activity against four organisms viz. Staphylococcus aureus (Gram positive), S. epidermidis (Gram positive), Bacillus subtilis (Gram positive), Escherichia coli (Gram negative) using amoxicillin as standard control. Compounds 4d, 6b, 6c have shown best antibacterial activity in the series. The antiproliferative activity was tested against human skin cancer cell line G361. The compounds 3d, 4d, 5b, 5d, 5e, 6c, 7a were found to be the best of the series and showed the activity at micromolar concentration.