Novel tricyclic inhibitors of IKK2: discovery and SAR leading to the identification of 2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl)pyridin-2-yl)methyl)acetamide (BMS-066)

  • Bioorg Med Chem Lett. 2011 Dec 1;21(23):7006-12. doi: 10.1016/j.bmcl.2011.09.111.
Scott H Watterson  1 ,  Charles M Langevine ,  Katy Van Kirk ,  James Kempson ,  Junquing Guo ,  Steven H Spergel ,  Jagabandhu Das ,  Robert V Moquin ,  Alaric J Dyckman ,  David Nirschl ,  Kurt Gregor ,  Mark A Pattoli ,  XiaoXia Yang ,  Kim W McIntyre ,  Guchen Yang ,  Michael A Galella ,  Hollie Booth-Lute ,  Laishun Chen ,  Zheng Yang ,  David Wang-Iverson ,  Murray McKinnon ,  John H Dodd ,  Joel C Barrish ,  James R Burke ,  William J Pitts
Affiliations
  • 1. Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 22018461 DOI: 10.1016/j.bmcl.2011.09.111
Abstract

The synthesis, structure-activity relationships (SAR), and biological results of pyridyl-substituted azaindole based tricyclic inhibitors of IKK2 are described. Compound 4m demonstrated potent in vitro potency, acceptable pharmacokinetic and physicochemical properties, and efficacy when dosed orally in a mouse model of Inflammatory Bowel Disease.