103548-09-0Relevant articles and documents
Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors
Seal, Jonathan T.,Atkinson, Stephen J.,Bamborough, Paul,Bassil, Anna,Chung, Chun-Wa,Foley, James,Gordon, Laurie,Grandi, Paola,Gray, James R. J.,Harrison, Lee A.,Kruger, Ryan G.,Matteo, Jeanne J.,McCabe, Michael T.,Messenger, Cassie,Mitchell, Darren,Phillipou, Alex,Preston, Alex,Prinjha, Rab K.,Rianjongdee, Francesco,Rioja, Inmaculada,Taylor, Simon,Wall, Ian D.,Watson, Robert J.,Woolven, James M.,Wyce, Anastasia,Zhang, Xi-Ping,Demont, Emmanuel H.
, p. 10772 - 10805 (2021/07/31)
The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole 23 (GSK809) and furan 24 (GSK743) that were derived from the pyrrole fragment 6. We transpose the key learnings from a previous pyridone series (GSK620 2 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research.
PYRAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS
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Page/Page column 70, (2018/09/21)
The present invention is directed to pyrazole derivatives, pharmaceutical compositions comprising the compounds and the use of the compounds or the compositions in the treatment of various diseases
Microstructure analysis of a CO2 copolymer from styrene oxide at the diad level
Wu, Guang-Peng,Zu, Yu-Ping,Xu, Peng-Xiang,Ren, Wei-Min,Lu, Xiao-Bing
, p. 1854 - 1862 (2013/09/02)
A large amount of interesting information on the alternating copolymerization of CO2 with terminal epoxides has already been reported, such as the regiochemistry of epoxide ring-opening and the stereochemistry of the carbonate unit sequence in the polymer chain. Moreover, the microstructures of CO2 copolymers from propylene oxide and cyclohexene oxide have also been well-studied. However, the microstructure of the CO2 copolymer from styrene oxide (SO), an epoxide that contains an electron-withdrawing group, has not yet been investigated. Herein, we focus on the spectroscopic assignment of the CO2 copolymer from styrene oxide at the diad level by using three kinds of model dimer compounds, that is, T-T, H-T, and H-H. By comparing the signals in the carbonyl region, we concluded that the signals at δ=154.3, 153.8, and 153.3 ppm in the 13C NMR spectrum of poly(styrene carbonate) were due to tail-to-tail, head-to-tail, and head-to-head carbonate linkages, respectively. Moreover, various isotactic and syndiotactic model compounds based on T-T, H-T, and H-H (dimers (R,R)-T-T, (S,S)-T-T, and (R,S)-T-T; (R,R)-H-T, (S,S)-H-T, and (R,S)-H-T; (R,R)-H-H, (S,S)-H-H, and (R,S)-H-H) were synthesized for the further spectroscopic assignment of stereospecific poly(styrene carbonate)s. We found that the carbonate carbon signals were sensitive towards the stereocenters on adjacent styrene oxide ring-opening units. These discoveries were found to be well-matched to the microstructures of the stereoregular poly(styrene carbonate)s that were prepared by using a multichiral CoIII-based catalyst system. T-T races: The spectroscopic assignment of regio- and stereoregular poly(styrene carbonate)s at the diad level was performed by 13C NMR studies of three kinds of model compounds, as well as their syndiotactic (R,S) and isotactic (R,R or S,S) dimers. Copyright
