5334-29-2

Usage

Uses

As the specific uses and effects of 1-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-OL are still being studied, the following applications are based on its potential and areas of interest in research:
Used in Pharmaceutical Research:
1-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-OL is used as a compound of interest for its potential biological activities, which may lead to the development of new drugs or therapeutic agents. Its unique structure and properties could contribute to the discovery of novel treatments for various diseases and conditions.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 1-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-OL is utilized for its potential to interact with biological targets, such as enzymes, receptors, or other proteins. This interaction could result in the modulation of biological processes, making it a candidate for the development of new pharmaceuticals.
Used in Chemical Research:
1-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-OL is employed in chemical research to explore its properties, reactivity, and potential applications in various chemical processes. Its unique structure may offer insights into the development of new synthetic routes or the creation of novel chemical compounds.

InChI:InChI=1/C11H7ClN4O/c12-7-1-3-8(4-2-7)16-10-9(5-15-16)11(17)14-6-13-10/h1-6,15H

Upstream product

• 50427-79-7 5-amino-1-(4-chlorophenyl)-1H-pyrazole-4-carboxamide 
• 123-06-8 Ethoxymethylenemalononitrile 
• 78972-85-7 1-(4-Chlor-phenyl)-5<(dimethylamino)methylenamino>-4-pyrazolcarbonitril 
• 52709-56-5 3-Chloro-5-dimethylamino-2-formyl-4-aza-2,4-pentadienenitrile 
• 1073-69-4 N-4-chlorophenylhydrazine 
• 77287-34-4 formamide 
• 14678-87-6 ethyl 5-amino-1-(4-chlorophenyl)-1H-pyrazole-4-carboxylate 
• 64-18-6 formic acid 
• 51516-67-7 5-amino-1-(4'-chlorophenyl)pyrazole-4-carbonitrile 
• 68-12-2 N,N-dimethyl-formamide 
• 1073-70-7 4-chlorophenylhydrazine hydrochloride 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 

Downstream Products

• 5334-59-8 4-chloro-1-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine 

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.

Synthesis and anti-Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives

Nine 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives with different substituents in the 4-position of the phenyl group and benzenesulfonamide moiety were synthesized and evaluated against Plasmodium falciparum. Six compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 5.13 to 12.22 μM. The most active derivative with substituents R1 = F / R2 = CH3 exhibited an IC50 value of 5.13 μM and an IS value of 62.90, which was higher than that of the control drug sulfadoxine. For this reason, it is possible to conclude that the 1H-pyrazolo[3,4-d]pyrimidine system is promising as a prototype for further studies of antimalarial candidates.

Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents

A series of hybrid aza heterocycles containing pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazole scaffold were synthesized from 1,3-dipolar cycloaddition reaction of pyrazolopyrimidinone based alkyne with azides using Cu(II) catalyst in presence of sodium ascorbate and evaluated for their anticancer efficacy in vitro against C6 rat and U87 human glioma cell lines. These compounds induced a concentration dependent inhibition of C6 rat and U87 human glioma cell proliferation. Compound 5f arrested the cells at S-phase of the cell cycle and induced apoptosis in U87 GBM cell lines. Further, apoptosis was evidenced by the cleavage of Caspase-3, PARP and up regulation of p53. In silico docking studies reveal that the compounds 5a, 5f and 5l were more effective in binding with TGFBR2 than other compounds.

Synthesis and in vitro antiproliferative activity of novel pyrazolo[3,4-d]pyrimidine derivatives

A novel series of pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity. Among the five compounds selected by NCI, compound 11a showed a distinctive pattern of selectivity on cell line panels and was further screened for a 5-log dose range, where it showed potent antiproliferative activity with median growth inhibition (GI50) equal to 1.71 μM against the CNS cancer SNB-75 cell line. The tested derivative showed remarkably the highest cell growth inhibition against non-small cell lung cancer HOP-62, CNS cancer SNB-75, breast cancer HS578T, and melanoma MALME-3M cell lines. Flow cytometric analysis revealed that compound 11a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. Further investigation showed that compound 11a induced significant cell cycle arrest at G0/G1 phase partly due to its ability to downregulate cyclin D1 and upregulate p27kip1 levels.

Synthesis of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines from 4,6-dichloropyrimidine-5-carboxaldehyde: Insights into selectivity and reactivity

Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5- carboxaldehyde with both aromatic and aliphatic hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines in a selective, high-yielding, and operationally simple manner are presented. For aromatic hydrazines, the reaction is performed at a high temperature in the absence of an external base. For aliphatic hydrazines, the reaction proceeds at room temperature in the presence of an external base. The observed selectivity and reactivity trends are rationalized through consideration of the proposed reaction mechanism. The 1-substituted 4-chloropyrazolo[3,4-d]pyrimidine products serve as versatile synthetic intermediates, through further functionalization of the 4-chloride moiety, enabling the rapid generation of a structurally diverse array of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines. Georg Thieme Verlag Stuttgart. New York.

Heterocyclic synthesis with nitriles: Synthesis of pyrazolopyrimidine and pyrazolopyridine derivatives

The reaction of N1-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d] pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed. Copyright Taylor & Francis Group, LLC.

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.

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.