Azabenzthiazole inhibitors of leukotriene A4 hydrolase

Authors :: Tanis, Virginia M.
Bacani, Genesis M.
Blevitt, Jonathan M.
Chrovian, Christa C.
Crawford, Shelby
De Leon, Aimee
Fourie, Anne M.
Gomez, Laurent
Grice, Cheryl A.
Herman, Krystal
Kearney, Aaron M.
Landry-Bayle, Adrienne M.
Lee-Dutra, Alice
Nelson, Jay
Riley, Jason P.
Santillán, Alejandro
Wiener, John J.M.
Xue, Xiaohua
Young, Arlene L.
Source :: Bioorganic & Medicinal Chemistry Letters. Dec2012, Vol. 22 Issue 24, p7504-7511. 8p.
Publication Year :: 2012
Abstract: Abstract: 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 =3–6nM and hERG Dofetilide Binding IC50 =8.9–> >10μM. [Copyright &y& Elsevier]