102503-23-1Relevant articles and documents
Synthetic studies to help elucidate the metabolism of the preclinical candidate TBAJ-876—a less toxic and more potent analogue of bedaquiline
Choi, Peter J.,Conole, Daniel,Sutherland, Hamish S.,Blaser, Adrian,Tong, Amy S.T.,Cooper, Christopher B.,Upton, Anna M.,Palmer, Brian D.,Denny, William A.
, (2020)
Bedaquiline is a novel drug approved in 2012 by the FDA for treatment of drug-resistant tuberculosis (TB). Although it shows high efficacy towards drug-resistant forms of TB, its use has been limited by the potential for significant side effects. In particular, bedaquiline is a very lipophilic compound with an associated long terminal half-life and shows potent inhibition of the cardiac potassium hERG channel, resulting in QTc interval prolongation in humans that may result in cardiac arrhythmia. To address these issues, we carried out a drug discovery programme to develop an improved second generation analogue of bedaquiline. From this medicinal chemistry program, a candidate (TBAJ-876) has been selected to undergo further preclinical evaluation. During this evaluation, three major metabolites arising from TBAJ-876 were observed in several preclinical animal models. We report here our synthetic efforts to unequivocally structurally characterize these three metabolites through their independent directed synthesis.
METALLOENZYME INHIBITOR COMPOUNDS
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Page/Page column 301, (2018/09/28)
Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.
Synthesis of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A2A receptor antagonists
Cole, Andrew G.,Stauffer, Tara M.,Rokosz, Laura L.,Metzger, Axel,Dillard, Lawrence W.,Zeng, Wenguang,Henderson, Ian
scheme or table, p. 378 - 381 (2011/03/18)
The discovery and synthesis of a series of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A2A receptor antagonists from a small-molecule combinatorial library using a high-throughput radioligand-binding assay is described. Antagonists were