69085-00-3

Upstream product

• 100-19-6 (4-nitrophenyl)ethanone 
• 99-81-0 4-Nitrophenacyl bromide 
• 6097-21-8 2-(4-nitrophenyl)-2-oxoethyl thiocyanate 
• 2104-08-7 4-(4-nitrophenyl)-2-oxo-thiazole 

Downstream Products

• 1435385-82-2 C₁₃H₁₀N₂O₃S₃ 

Relevant academic research and scientific papers

A kind of two-thiazoline ketone compounds and pharmaceutical compositions thereof and use thereof (by machine translation)

The invention provides general formula (I) indicated by the thiazoline ketone compounds and pharmaceutical compositions thereof and use thereof. The compounds can be combined with the bromodomain domain of the protein, thereby adjusting the downstream signal path, to play a particular function, can be used for treating the relevant domain protein in the bromodomain of various diseases. Such compounds can be interference has Brd4 bromodomain domain with the acetylated histone binding, and then lower the oncogene c - the ventilating cabins and its related target gene transcription, so that it may be effective for treating the tumor. (by machine translation)

Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain

Recognizing acetyllysine of histone is a vital process of epigenetic regulation that is mediated by a protein module called bromodomain. To contribute novel scaffolds for developing into bromodomain inhibitors, we utilize a fragment-based drug discovery approach. By successively applying docking and X-ray crystallography, we were able to identify 9 fragment hits from diffracting more than 60 crystals. In the present work, we described four of them and carried out the integrated lead optimization for fragment 8, which bears a 2-thiazolidinone core. After several rounds of structure guided modifications, we assessed the druggability of 2-thiazolidinone by modulating in vitro pharmacokinetic studies and cellular activity assay. The results showed that two potent compounds of 2-thiazolidinones have good metabolic stability. Also, the cellular assay confirmed the activities of 2-thiazolidinones. Together, we hope the identified 2-thiazolidinone chemotype and other fragment hits described herein can stimulate researchers to develop more diversified bromodomain inhibitors.