927671-03-2

Upstream product

• 927672-57-9 3-(4-methoxyphenylamino)phthalic acid 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 87-59-2 2,3-Dimethylaniline 
• 31599-60-7 1-iodo-2,3-dimethylbenzene 
• 28418-88-4 3-iodophthalic anhydride 
• 959150-64-2 (RS)-2-(2,6-dioxopiperidin-3-yl)-4-iodoisoindole-1,3-dione 
• 104-94-9 4-methoxy-aniline 
• 835616-60-9 2‐(2,6‐dioxopiperidin‐3‐yl)‐4‐fluoroisoindoline‐1,3‐dione 

Relevant academic research and scientific papers

Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries

Current methods for the preparation of heterobifunctional pomalidomide-conjugates rely on methods that are often low yielding and produce intractable byproducts. Herein we describe our strategy for the reliable and succinct preparation of pomalidomide-linkers which is essential to the formation of these conjugates. We present the preparation of 18 pomalidomide-linkers in high yield compared to current literature methods. Our findings show that secondary amines consistently afford greater yields than their primary counterparts, a trend that we were able to exploit in the synthesis of several new pomalidomide homo-dimers in enhanced yields compared to similar literature syntheses. This trend was further utilised to develop the first one-pot synthesis of JQ1-pomalidomide conjugates in yields up to 62%, providing a method that is suited to rapid preparation of conjugate libraries as is frequently required for the development of new protein degraders.

In pursuit of a selective hepatocellular carcinoma therapeutic agent: Novel thalidomide derivatives with antiproliferative, antimigratory and STAT3 inhibitory properties

Advanced stage liver cancer is predominantly treated with the multi-kinase inhibitor sorafenib; however, this therapeutic agent lacks selectivity in its cytotoxic actions and is associated with poor survival outcomes. Herein we report the design and preparation of several thalidomide derivatives, including a variety of novel thioether-containing forms that are especially rare in the literature. Importantly, two of the derivatives described are potent antiproliferative agents with dose-dependent selectivity for tumorigenic liver progenitor cells (LPC) growth inhibition (up to 36% increase in doubling time at 10 μM) over non-tumorigenic cells (no effect at 10 μM). Furthermore, these putative anti-liver cancer agents were also found to be potent inhibitors of tumorigenic LPC migration. This report also describes these derivatives’ effects on several key signalling pathways in our novel liver cell lines by immunofluorescence and AlphaLISA assays. Aryl thioether derivative 7f significantly reduced STAT3 phosphorylation (23%) and its nuclear localisation (16%) at 10 μM in tumorigenic LPCs, implicating the IL-6/JAK/STAT3 axis is central in the mode of action of our derivatives.

Isoindole-imide compounds and compositions comprising and methods of using the same

This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.