| Autor: |
Graham Smith, Michael D. Altman, Larissa Rakhilina, Dietrich Steinhuebel, Jason D. Brubaker, Craig R. Gibeau, John Maclean, Ruojing Yang, Erin F. Mulrooney, Hongmin Chen, James Baker, Charles A. Lesburg, Jeremy Presland, Lily Y. Moy, Melanie A. Kleinschek, Yiping Chen, Thierry O. Fischmann, Jongwon Lim, Erica Leccese |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
ACS Medicinal Chemistry Letters. 6:683-688 |
| ISSN: |
1948-5875 |
| Popis: |
Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential signal transducer downstream of the IL-1R and TLR superfamily, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides was developed via sequential modifications to the 5-position of the pyrazolopyrimidine ring and the 3-position of the pyrazole ring. Replacement of substituents responsible for poor permeability and improvement of physical properties guided by cLogD led to the identification of IRAK4 inhibitors with excellent potency, kinase selectivity, and pharmacokinetic properties suitable for oral dosing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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