650628-21-0

Upstream product

• 1429924-41-3 4,6-dichloro-5-((2-(2-methoxyphenyl)hydrazono)methyl)pyrimidine 
• 6971-45-5 2-methoxyphenylhydrazine hydrochloride 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 
• 18312-46-4 (2-methoxyphenyl)hydrazine 
• 650628-20-9 1-(2-methoxy-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 

Downstream Products

• 791781-10-7 [1-(2-methoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-hydrazine 
• 1207760-61-9 4-Methoxy-2-{[1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}-N-(5-methylpyridin-2-yl)butanamide 

Relevant academic research and scientific papers

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.

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.

PYRAZOLOPYRIMIDINES AS KINASE INHIBITORS

The present invention relates generally to inhibitors of the kinases and more particularly to novel pyrazolopyrimidine compounds.