221006-70-8Relevant 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.
, (2020/03/26)
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.
ANTIBACTERIAL COMPOUNDS AND USES THEREOF
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Paragraph 0111, (2017/09/28)
The present invention relates to compounds of formula (I) including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of tuberculosis.
Towards compatibility between ruthenium sensitizers and cobalt electrolytes in dye-sensitized solar cells
Polander, Lauren E.,Yella, Aswani,Curchod, Basile F. E.,Ashari Astani, Negar,Teuscher, Joel,Scopelliti, Rosario,Gao, Peng,Mathew, Simon,Moser, Jacques-E.,Tavernelli, Ivano,Rothlisberger, Ursula,Graetzel, Michael,Nazeeruddin, Md. Khaja,Frey, Julien
supporting information, p. 8731 - 8735 (2013/09/12)
Ruthenium and Co: Ruthenium(II) complexes remain prime candidates for dye-sensitized solar applications; however, current ruthenium sensitizers are not compatible with cobalt(II/III) electrolytes. Herein, the effect of surface insulation on device efficiency is studied by comparing two cyclometalated tris-heteroleptic ruthenium(II) complexes. This approach demonstrates a general principle that leads to unprecedented efficiency for a ruthenium(II) sensitizer used in combination with a cobalt electrolyte. Copyright
