64436-92-6Relevant articles and documents
Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel
Yu, Zhiyi,Van Veldhoven, Jacobus P.D.,'T Hart, Ingrid M.E.,Kopf, Adrian H.,Heitman, Laura H.,Ijzerman, Adriaan P.
supporting information, p. 50 - 59 (2015/11/23)
We synthesized and evaluated a series of compounds for their allosteric modulation at the Kv11.1 (hERG) channel. Most compounds were negative allosteric modulators of [3H]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known Kv11.1 blockers.
Ligandless copper-catalyzed coupling of heteroaryl bromides with gaseous ammonia
Fantasia, Serena,Windisch, Johannes,Scalone, Michelangelo
supporting information, p. 627 - 631 (2013/04/11)
A range of different N- and S-containing heterocyclic bromides can be efficiently coupled with gaseous ammonia in the presence of copper(II) acetylacetonate [Cu(acac)2] as catalyst and in the absence of additional ligands. Unstable aminothiophenes and aminobenzothiophenes can be further reacted in situ to afford functionalized derivatives. Copyright
Process development of a novel azetidinyl ketolide antibiotic
Li, Bryan,Magee, Thomas V.,Buzon, Richard A.,Widlicka, Daniel W.,Bill, Dave R.,Brandt, Thomas,Cao, Xiaoping,Coutant, Michael,Dou, Haijian,Granskog, Karl,Flanagan, Mark E.,Hayward, Cheryl M.,Li, Bin,Liu, Fengwei,Liu, Wei,Nguyen, Thuy-Trinh,Raggon, Jeffrey W.,Rose, Peter,Rainville, Joseph,Reilly, Usa Datta,Shen, Yue,Sun, Jianmin,Wilcox, Glenn E.
scheme or table, p. 788 - 797 (2012/08/27)
Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.
