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Usage

General Description

4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-1-(4-methylphenyl)- is a chemical compound with the molecular formula C15H13N3O. It is a derivative of pyrazolopyrimidine and is known for its potential pharmaceutical applications. 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-1-(4-methylphenyl)- is a heterocyclic organic compound that contains a pyrazolo[3,4-d]pyrimidine skeleton with a dihydro-1-(4-methylphenyl)- substitution. It has been studied for its potential use in the treatment of various diseases, including cancer and neurological disorders, and has shown promising pharmacological activity in preclinical studies. Additionally, it is also used as a reagent in organic synthesis for the preparation of novel compounds with potential therapeutic benefits.

Upstream product

• 100061-56-1 (5-amino-1-p-tolyl-1H-pyrazole-4-carboxamide) 
• 123-06-8 Ethoxymethylenemalononitrile 
• 103646-82-8 5-amino-1-(4-methylphenyl)pyrazole-1-carbonitrle 
• 539-44-6 N-4-methylphenylhydrazine 
• 52709-56-5 3-Chloro-5-dimethylamino-2-formyl-4-aza-2,4-pentadienenitrile 
• 152992-58-0 5-Amino-4-cyano-1-p-tolyl-1H-pyrazole-3-carboxylic acid ethyl ester 
• 132815-69-1 (Z)-ethyl-2-chloro-2-(2-(p-tolyl)-hydrazono)acetate 
• 64-18-6 formic acid 
• 152992-77-3 4-Oxo-1-p-tolyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid 

Downstream Products

• 650628-55-0 (1-p-tolyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-hydrazine 

Relevant academic research and scientific papers

New pyrazolopyrimidine derivatives as Leishmania amazonensis arginase inhibitors

Arginase performs the first enzymatic step in polyamine biosynthesis in Leishmania and represents a promising target for drug development. Polyamines in Leishmania are involved in trypanothione synthesis, which neutralize the oxidative burst of reactive oxygen species (ROS) and nitric oxide (NO) that are produced by host macrophages to kill the parasite. In an attempt to synthesize arginase inhibitors, six 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents at the 4-position of the phenyl group were synthesized. All compounds were initially tested at 100 μM concentration against Leishmania amazonensis ARG (LaARG), showing inhibitory activity ranging from 36 to 74%. Two compounds, 1 (R=H) and 6 (R=CF3), showed arginase inhibition >70% and IC50 values of 12 μM and 47 μM, respectively. Thus, the kinetics of LaARG inhibition were analyzed for compounds 1 and 6 and revealed that these compounds inhibit the enzyme by an uncompetitive mechanism, showing Kis values, and dissociation constants for ternary complex enzyme-substrate-inhibitor, of 8.5 ± 0.9 μM and 29 ± 5 μM, respectively. Additionally, the molecular docking studies proposed that these two uncompetitive inhibitors interact with different LaARG binding sites, where compound 1 forms more H-bond interactions with the enzyme than compound 6. These compounds showed low activity against L. amazonensis free amastigotes obtained from mice lesions when assayed with as much as 30 μM. The maximum growth inhibition reached was between 20 and 30% after 48 h of incubation. These results suggest that this system can be promising for the design of potential antileishmanial compounds.

Identification of novel GLUT inhibitors

The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure–activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging.

Some pyrazole and pyrazolo[3,4-d]pyrimidine derivatives: Synthesis and anticancer evaluation

5-Amino-1-p-tolyl-1H-pyrazole-4-carbonitrile (1) was used for the preparation of some novel pyrazoles and pyrazolo[3,4-d]pyrimidines 2-10. Moreover, the cytotoxicity and in vitro anticancer activities of the prepared compounds were also assessed against the MCF-7 breast cancer, HepG2 liver cancer, and A549 lung carcinoma cell lines, along with investigation of the effect of the synthesized compounds on the expression of urokinase plasminogen activator (uPA). The tested compounds exhibited remarkable cytotoxic activity against MCF-7 and HepG2 cells. Among the tested compounds, 2 and 9 revealed promising anticancer activity compared to the activity of the commonly used anticancer drug, doxorubicin, by inhibiting the expression of uPA.

Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar1) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range.

Reaction of 5-aminopyrazole derivatives with ethoxymethylene- malononitrile and its analogues

A one-pot synthesis using 5-aminopyrazole derivatives 1 with ethoxymethylenemalononitrile (EMMN), ethyl ethoxymethylenecyanoacetate (EMCA) or diethyl ethoxymethylenemalonate (DEMM) gave pyrazolo-[1,5-a]pyrimidine compounds 2,4,8. Also, the one step reaction of EMCA with hydrazine hydrate afforded ethyl(4-ethoxycarbonyl-5-pyrazolyl)aminomethylenecyanoacetate 3c. On the other hand, the reaction of 1-substituted 5-aminopyrazole-4-carboxamide 9 with EMMN afforded pyrazolo[3,4-d]pyrimidine compounds 10.

Heterocyclic Synthesis Using Hydrazonoyl Halides: Synthesis of Annelated Pyrimidines, Pyridazines and Pyrazoles

Aminocyanopyrazoles and dihydropyrrolopyrazole-4,6-diones were obtained in good yields by the reaction of hydrazonoyl halides with malononitrile and N-arylmaleimides respectively. Pyrazolopyrimidines and pyrazolopyridazines were synthesized in quantitative yields by the reaction of formic acid or formamide and hydrazine hydrate with aminocyanopyrazoles. Novel ring systems, 4-mercapto-1,2,3,5,6,7-hexaazaacenaphthylenes 20 and 7-thia-1,2,4,5,6,10-hexaazacyclopentacenaphthylenes 22 were prepared by the reaction of 18 with carbon disulfide and the reaction of 21 with acetic anhydride. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data and alternate synthesis wherever possible.

3-Chlor-5-dimethylamino-2-formyl-4-aza-2,4-pentadiennitril, Synthese und Umsetzungen mit Nucleophilen

3-Chloro-5-dimethylamino-2-formyl-4-aza-2,4-pentadienenitrile (7) is prepared by partial hydrolysis of the iminium perchlorate 1.In 7 the electrophilic centres (1, 3, 5) regioselectively react with secondary alkylamines, arylamines, and hydrazine derivatives to yield 3-amino-substituted formylazapentadienenitriles and (hydrazonomethyl)azapentadienenitriles.Intramolecular cyclisation leads to triazole betaines, pyrazoles, and 1,4-dihydropyrimidines.