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)
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- 作者：Scott H. ; Watterson ; ; ; scott.watterson@bms.com ; 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
- 关键词：IKK ; IKK2 ; IKK¦Â ; NF-¦ÊB ; BMS-066
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2011
- 出版时间：1 December 2011
- 年：2011
- 卷：21
- 期：23
- 页码：7006-7012
- 全文大小：933 K
文摘
The synthesis, structure¨Cactivity 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.