23000-47-7

Usage

Uses

Used in Pharmaceutical Industry:
4-CHLORO-1-(P-TOLYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE is used as a research and development compound for the synthesis of potential drug candidates. Its unique structure allows for the development of new molecules with potential therapeutic applications.
Used in Agrochemical Industry:
4-CHLORO-1-(P-TOLYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE is also used in the agrochemical industry for the synthesis of crop protection chemicals. Its reactivity and molecular structure contribute to the development of innovative solutions for agricultural challenges.

Upstream product

• 1429924-43-5 4,6-dichloro-5-((2-p-tolylhydrazono)methyl)pyrimidine 
• 637-60-5 p-tolylhydrazine hydrochloride 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 
• 539-44-6 N-4-methylphenylhydrazine 
• 103646-82-8 5-amino-1-(4-methylphenyl)pyrazole-1-carbonitrle 

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.

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.

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.

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.

Selective synthesis of 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines

Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5- carboxaldehyde with various hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines in a selective and high-yielding manner are presented. For aromatic hydrazines, the reaction is performed in the absence of an external base, which promotes exclusive hydrazone formation. The hydrazones subsequently cyclize at an elevated temperature to form the desired pyrazolo[3,4-d]pyrimidine products. For aliphatic hydrazines, the reaction sequence proceeds as a single step in the presence of an external base.

PYRAZOLOPYRIMIDINES AS ANTI - HEPATITS C AGENTS

Pyrazolopyrimidine derivatives of formula (I), or a pharmaceutically acceptable salt thereof, are found to be active against hepatitis C infection, wherein: R1 is C6-C10 aryl, 5- to 10- membered heteroary1, -(C1-C4 alkyl)-(C6-C10 aryl) or -(C1-C4 alkyl)-(5- to 10- membered heteroaryl); R2 is a C6-C10 aryl, C3-C6 carbocyclyl, 5- to 10- membered heteroaryl or 5- to 10- membered heterocyclyl moiety, said moiety being optionally fused to a C6-C10 aryl, C3-C6 carbocyclyl, 5- to 10- membered heteroaryl or 5- to 10-membered heterocyclic ring; and X is -NR'-, -NR'-CO-NR''-, -NR'-L, or -NR'-CO-L-, wherein R' and R'' are the same or different and each represent hydrogen or a C1-C6 alkyl group and L represents a C1-C6 alkylene group, the aryl, heteroaryl, heterocyclyl. and carbocyclyl moieties in the R1 and R2 substituents being unsubstituted or substituted by 1, 2 or 3 substituents selected from halogen, C1-C4 alkyl C1-C4alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano, nitro, C6-C10 aryl, C3-C6 carbocyclyl, 5- to 10- membered heterocyclyl, 5- to 10- membered heteroaryl, -NR'-CO2-R'', -CO2R'', -COR'''-NR'-CO-R''',-CONR'R'',SO2NR'R'',SO2R'''and -O-(CH2)n-R''' substituents, wherein n is from 0 to 4, each R’is the same or different and is hydrogen or C1-C6 alkyl, each R'' is the same or different and is hydrogen, C1-C6 alkyl, C6-C10 aryl, 5- to 10- membered heterocyclyl or 5- to 10- membered heteroaryl, each R''' is the same or different and is C1-C6 alkyl, C6-C10 aryl, 5- to 10- membered heterocyclyl or 5- to 10- membered heteroaryl, and each R'''' is the same or different and is C6-C10 aryl, 5- to 10- membered heterocyclyl or 5- to 10- membered heterocryl, the aryl, heteroaryl, heterocyclyl and carbocyclyl moieties in said substituents being unsubstituted or substituted by a further substituent selected from C1-C4 alkyl, C1-C4 hydroxyalkyl and C1-C4 haloalkyl groups.

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.