1283719-20-9Relevant academic research and scientific papers
Aiming to Miss a Moving Target: Bromo and Extra Terminal Domain (BET) Selectivity in Constrained ATAD2 Inhibitors
Bamborough, Paul,Chung, Chun-Wa,Furze, Rebecca C.,Grandi, Paola,Michon, Anne-Marie,Watson, Robert J.,Mitchell, Darren J.,Barnett, Heather,Prinjha, Rab K.,Rau, Christina,Sheppard, Robert J.,Werner, Thilo,Demont, Emmanuel H.
, p. 8321 - 8336 (2018)
ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of its class. In our recent disclosure of the first chemical probe against this bromodomain, GSK8814 (6), we described the use of a conformationally constrained methoxy piperidine to gain selectivity over the BET bromodomains. Here we describe an orthogonal conformational restriction strategy of the piperidine ring to give potent and selective tropane inhibitors and show structural insights into why this was more challenging than expected. Greater understanding of why different rational approaches succeeded or failed should help in the future design of selectivity in the bromodomain family.
CYCLOALKYL-SUBSTITUTED PYRIMIDINEDIONE COMPOUNDS
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Paragraph 0076, (2015/01/07)
The present invention provides novel cycloalkyl-substituted pyrimidine dione compounds that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds is described, as well as methods for treating HCM and other forms of heart disease.
