1255652-75-5

Upstream product

• 1236151-75-9 ethyl 2-(2-((tert-butoxycarbonyl)amino)-6-chloro-9H-purin-9-yl)acetate 
• 1255652-18-6 ethyl 2-(2-((tert-butoxycarbonyl)(4-cyclohexylbenzyl)amino)-6-chloro-9H-purin-9-yl)acetate 
• 1255652-40-4 ethyl 2-(2-((tert-butoxycarbonyl)(4-cyclohexylbenzyl)amino)-6-(cyclohexylamino)-9Hpurin-8-yl)acetate 
• 208259-47-6 4-cyclohexylphenylmethyl alcohol 
• 108-91-8 cyclohexylamine 
• 10310-21-1 2-amino-6-chloropurine 

Downstream Products

• 1255653-15-6 2-(6-(cyclohexylamino)-2-((4-cyclohexylbenzyl)amino)-9H-purin-9-yl)acetic acid 

Relevant academic research and scientific papers

Identification of purine-scaffold small-molecule inhibitors of stat3 activation by QSAR studies

To facilitate the discovery of clinically useful Stat3 inhibitors, computational analysis of the binding to Stat3 of the existing Stat3 dimerization disruptors and quantitative structure-activity relationships (QSAR) were pursued, by which a pharmacophore model was derived for predicting optimized Stat3 dimerization inhibitors. The 2,6,9-trisubstituted-purine scaffold was functionalized in order to access the three subpockets of the Stat3 SH2 domain surface and to derive potent Stat3-binding inhibitors. Select purine scaffolds showed good affinities (KD, 0.8-12 μM) for purified, nonphosphorylated Stat3 and inhibited Stat3 DNA-binding activity in vitro and intracellular phosphorylation at 20-60 μM. Furthermore, agents selectively suppressed viability of human prostate, breast and pancreatic cancer cells, and v-Src-transformed mouse fibroblasts that harbor aberrant Stat3 activity. Studies herein identified novel small-molecule trisubstituted purines as effective inhibitors of constitutively active Stat3 and of the viability of Stat3-dependent tumor cells, and are the first to validate the use of purine bases as templates for building novel Stat3 inhibitors.

SUBSTITUTED 2-(9H-PURIN-9-YL) ACETIC ACID ANALOGUES AS INHIBITORS OF STAT3

In one aspect, the invention relates to substituted purine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.