Title of article
Pyrazolo-pyrimidines: A novel heterocyclic scaffold for potent and selective p38α inhibitors
Author/Authors
Jagabandhu Das، نويسنده , , Robert V. Moquin، نويسنده , , Sidney Pitt، نويسنده , , Rosemary Zhang، نويسنده , , Ding Ren Shen، نويسنده , , Kim W. McIntyre، نويسنده , , Kathleen Gillooly، نويسنده , , Arthur M. Doweyko، نويسنده , , John S. Sack، نويسنده , , Hongjian Zhang، نويسنده , , Susan E. Kiefer، نويسنده , , Kevin Kish، نويسنده , , Murray McKinnon، نويسنده , , Joel C. Barrish، نويسنده , , John H. Dodd، نويسنده , , Gary L. Schieven، نويسنده , , Katerina Leftheris، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
6
From page
2652
To page
2657
Abstract
The synthesis and structure–activity relationships (SAR) of p38α MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2x was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38α is also disclosed.
Keywords
Pyrazolo-pyrimidines , p38? inhibitors
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
799424
Link To Document