3区 · 医学
Article
作者: Kerns, Jeffrey K. ; Busch-Petersen, Jakob ; Fu, Wei ; Boehm, Jeffrey C. ; Nie, Hong ; Muratore, Michael ; Bullion, Ann ; Lin, Guoliang ; Li, Huijie ; Davis, Roderick ; Lin, Xichen ; Lakdawala, Ami S. ; Cousins, Rick ; Field, Rita ; Payne, Jeremy ; Miller, David D. ; Bamborough, Paul ; Christopher, John A. ; Baldwin, Ian ; Osborn, Ruth R. ; Yonchuk, John ; Webb, Edward ; Rumsey, William L.
IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.