2104-08-7Relevant articles and documents
Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain
Zhao, Lele,Cao, Danyan,Chen, Tiantian,Wang, Yingqing,Miao, Zehong,Xu, Yechun,Chen, Wuyan,Wang, Xin,Li, Yanlian,Du, Zhiyan,Xiong, Bing,Li, Jian,Xu, Chunyan,Zhang, Naixia,He, Jianhua,Shen, Jingkang
, p. 3833 - 3851 (2013/07/11)
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.
A correlative IR, MS, 1H, 13C and 15 NMR and theoretical study of 4-arylthiazol-2(3H)-ones
Pihlaja, Kalevi,Ovcharenko, Vladimir,Kolehmainen, Erkki,Laihia, Katri,Fabian, Walter M.F.,Dehne, Heinz,Perjessy, Alexander,Kleist, Marion,Teller, Joachim,Sustekova, Zora
, p. 329 - 336 (2007/10/03)
Sixteen 4-arylthiazol-2(3H)-ones (3) were synthesised by cyclisation of α-thiocyanatoacetophenones (1) in acid solution. They appear to prefer greatly the oxo tautomeric forms. In CCI4 solution an equilibrium between the free C=O bond and a "di
