650628-53-8

Upstream product

• 116884-63-0 (5-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxamide) 
• 77287-34-4 formamide 
• 19501-58-7 4-methoxyphenylhydrazine hydrochloride 
• 5305-40-8 2,6-dichloro-pyrimidine carbaldehyde 
• 64-18-6 formic acid 
• 116884-64-1 (5-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carbonitrile) 
• 15001-13-5 ethyl 5-amino-1-(4-methoxy)phenyl-1H-pyrazole-4-carboxylate 
• 3471-32-7 4-Methoxyphenylhydrazine 

Downstream Products

• 1235035-96-7 4-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenol 
• 1235035-61-6 4-(4-(3-(dimethylamino)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenol 
• 650628-52-7 4-hydrazino-1-[4-methoxyphenyl]-1H-rzl[3,4-d]pyrimidine 
• 650628-54-9 4-chloro-1-(4-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine 

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.

Discovery of a potent and selective BCL-XLinhibitor with in vivo activity

A-1155463, a highly potent and selective BCL-XLinhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical liabilities. A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. A-1155463 thus represents an excellent tool molecule for studying BCL-XLbiology as well as a productive lead structure for further optimization.

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.

ANTIVIRAL PYRIMIDINES

Disclosed herein are novel compounds comprising substituted pyrimidines, pyrazolopyrimtdines, and imidazolopyrimidines, the syntheses thereof, and compositions thereof, including pharmaceutical compositions, comprising the novel pyrimidines, pyrazolopyrimtdines, imidazolpyrimidines and related compounds. Such compounds function to inhibit entry of viruses of the Flaviviridae family, including Hepatitis C virus (HCV), into cells that are susceptible to virus infection. These compounds are useful for the treatment, therapy and/or prophylaxis of viral diseases and infection, including HCV infection.

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.

PYRAZOLOPYRIMIDINES AS KINASE INHIBITORS

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

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.