885524-07-2

Basic information

• Product Name: 4-CHLORO-1-(4-FLUOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE
• Synonyms: AKOS BBS-00002138;4-CHLORO-1-(4-FLUOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE
• CAS NO: 885524-07-2
• Molecular Formula: C₁₁H₆ClFN₄
• Molecular Weight: 248.64
• Mol File: 885524-07-2.mol

Chemical Properties

• Boiling Point: 319.0±42.0 °C(Predicted)
• Appearance: /
• Density: 1.54±0.1 g/cm3(Predicted)
• PKA: 1.33±0.30(Predicted)
• CAS DataBase Reference: 4-CHLORO-1-(4-FLUOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CHLORO-1-(4-FLUOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE(885524-07-2)
• EPA Substance Registry System: 4-CHLORO-1-(4-FLUOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE(885524-07-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 885524-07-2(Hazardous Substances Data)

Upstream product

• 289651-72-5 1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol 
• 371-14-2 4-fluorophenylhydrazine 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 
• 823-85-8 4-fluorophenyhydrazine hydrochloride 
• 1429924-45-7 4,6-dichloro-5-((2-(4-fluorophenyl)hydrazono)methyl)pyrimidine 
• 289651-72-5 1-benzyl-5-(2,2-diethoxyethyl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one 
• 51516-70-2 5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile 

Downstream Products

• 890881-57-9 C₁₇H₁₈FN₅ 

Relevant articles and documents

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.

GLUCOSE TRANSPORT INHIBITORS

The present invention relates to chemical compounds of general formula (I): in which RA, RB, RC, RD, m, and n are as given in the description and in the claims, and which effectively and selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

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.

A one step synthesis of 1-alkylpyrazolo[5,4-d]pyrimidines

A new synthesis of 1-alkylpyrazolo[5,4-d]pyrimidines is described. The reaction of 4,6-dichloropyrimidine-5-carbaldehyde with various substituted hydrazines provides such compounds in a single step from commercially available starting materials. This method has advantages over methods currently described in the literature for the construction of such ring systems.

Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d]pyrimidines

General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization.