Portal de Periódicos da CAPES

Azabenzthiazole inhibitors of leukotriene A4 hydrolase

2012; Elsevier BV; Volume: 22; Issue: 24 Linguagem: Inglês

10.1016/j.bmcl.2012.10.036

1464-3405

Virginia M. Tanis, Genesis M. Bacani, Jonathan M. Blevitt, Christa C. Chrovian, Shelby Crawford, Aimee De Leon, Anne M. Fourie, Laurent Gomez, Cheryl A. Grice, Krystal Herman, Aaron M. Kearney, Adrienne M. Landry-Bayle, Alice Lee-Dutra, Jay A. Nelson, Jason P. Riley, Alejandro Santillán, John J. M. Wiener, Xiaohua Xue, Arlene L. Young,

Synthesis and Biological Evaluation

Previously, benzthiazole containing LTA4H inhibitors were discovered that were potent (1–3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering c Log D) a new benzthiazole series was designed, congeners of 1–3, which led to compounds 7a, 7c, 12a–d which exhibited LTA4H IC50 = 3–6 nM and hERG Dofetilide Binding IC50 = 8.9–> >10 μM.